BRAF V600 (Annotated)
This is the annotated version of BRAF V600. It is structurally equivalent to that example and includes inline YAML comments throughout the source file explaining the role and rationale of each field. This version is intended for readers learning to work with the Cat-VRS specification.
Source
CIViC variant id 17: BRAF V600
Recipes that this example satisfies
None
Properties
id: civic.vid:17CIViC Variant ID, where vid stands for Variant ID, derived from the Variant ID contained within the CIViC URL for this genomic alteration.
type: CategoricalVariantThis value is required by the specification for all Categorical Variant objects.
name: BRAF V600Human-readable name for this variant.
description: BRAF V600 variants are missense amino acid substitutions that result in a change at valine 600, with V600E being the most common and V600K, V600M, V600R, and V600G also observed.This field was populated with an example value because CIViC does not provide a longform description.
aliases: NM_004333.6(BRAF) V600, NM_004333.6 V600Example aliases that include the MANE Select transcript for BRAF were included.
extensions: CIViC Representative Variant CoordinatesGRCh37 genomic coordinates on chromosome 7.
mappings: V600E (c.1799T>A), V600R (c.1798_1799delinsAG), V600K (c.1798_1799delinsAA), V600G (c.1799T>G), V600M (c.1798G>A)ClinVar variants corresponding to amino acid substitutions at BRAF V600 were included as relatedMatch mappings.
- Defining Location Constraint
The defining location is amino acid position 600 within the BRAF protein (refseq:NP_004324.2), the protein product of the MANE Select coding transcript for BRAF (refseq:NM_004333.6), corresponding to valine in the reference sequence. The
matchCharacteristicis set to “is_within”, meaning any variant whose affected residue falls within this position satisfies the constraint.
Members
The members field includes five VRS Allele objects generated using the VICC Variation Normalizer from the hgvs.c representations of BRAF:
V600E (NM_004333.6:c.1799T>A)
V600K (NM_004333.6:c.1798_1799delinsAA)
V600G (NM_004333.6:c.1799T>G)
V600M (NM_004333.6:c.1798G>A)
V600R (NM_004333.6:c.1798_1799delinsAG)
Full example: JSON
Comments do not compile from yaml to json, so only the yaml version of this example is included on this page.
Full example: YAML
# Categorical Variants are described using the Cat-VRS data model, here:
# https://cat-vrs.readthedocs.io/en/latest/concepts/catvrs_model.html
# While Categorical Variants can be defined using any combination of constraints, the Cat-VRS development team
# is generating common types of Categorical Variants, named "recipes", and these can be found here:
# https://cat-vrs.readthedocs.io/en/latest/concepts/recipes.html
# Here, we describe the Protein Sequence Consequence Categorical Variant for BRAF V600 variants,
# referenced from CIViC: https://civicdb.org/variants/17/summary
# id: The ‘logical’ identifier of the Entity in the system of record, e.g. a UUID.
# This ‘id’ is unique within a given system, but may or may not be globally unique outside the system.
# Within these examples, we are using the nomenclature {originating resource}:{identifier that they are using}
# Given the URL https://civicdb.org/variants/17/summary, we will use the id of civic.vid:17
id: civic.vid:17
# type: All Categorical Variants must be of type 'CategoricalVariant'. This specifies the data type of the object.
type: CategoricalVariant
# name: A primary name for the entity. This is intended to be human-readable.
name: BRAF V600 (annotated)
# description: A free-text description of the entity
description: >-
BRAF V600 variants are missense amino acid substitutions that result in Valine changed.
V600E is the most common substitution, but V600K, V600M, V600R, and V600G have also been observed.
# aliases: Alternative names of the Categorical Variant. For most examples, we have filled in hgvs representations
# within aliases but hgvs requires an alternate allele to be specified, which we cannot do here. Thus we've just added
# a version of the name with the MANE Select transcript specified.
aliases:
- NM_004333.6(BRAF) V600
- NM_004333.6 V600
# extensions: A list of extensions to the Entity, that allow for capture of information not directly
# supported by elements defined in the model.
# The decision of how to structure extensions are left to implementers, though we recommend documenting an
# implementation's use of extensions in the Standard Operating Procedure to promote ease of use.
extensions:
- name: CIViC Representative Variant Coordinates
value:
chromosome: '7'
start: 140453136
stop: 140453137
reference_bases: ''
variant_bases: ''
representative_transcript: ENST00000288602.6
ensembl_version: 75
reference_build: GRCh37
# constraints: A rule or set of rules that must be satisfied for a Categorical Variant to be considered valid.
# The currently implemented constraints can be viewed online, here:
# https://cat-vrs.readthedocs.io/en/latest/concepts/catvrs_model.html#constraint
# They also can be viewed within the source yaml file, located at schema/cat-vrs/cat-vrs-source.yaml, within this
# GitHub repository.
# For each categorical variant there may be 0 to n constraints.
constraints:
# The DefiningLocationConstraint describes variation relative to a VRS location
# The VRS location can be transcribed in full, or abbreviated with the notation vrs.json#/ga4gh:VA...
- type: DefiningLocationConstraint
location:
id: ga4gh:SL.1ReS370wzmC9PGTn13XrnG8Ot7UAKYuw
description: Amino acid position 600 within the BRAF protein (refseq:NP_004324.2), which is the protein product of the MANE Select (GRCh38) coding transcript for BRAF (refseq:NM_004333.6), corresponding to valine in the reference sequence.
type: SequenceLocation
digest: 1ReS370wzmC9PGTn13XrnG8Ot7UAKYuw
sequenceReference:
id: refseq:NP_004324.2
name: NP_004324.2
description: The protein product of the MANE Select (GRCh38) coding transcript for BRAF (refseq:NM_004333.6), corresponding to the Refseq protein accession NP_004324.2.
aliases:
- ensembl:ENSP00000288602.6
- ga4gh:SQ.cQvw4UsHHRRlogxbWCB8W-mKD4AraM9y
type: SequenceReference
refgetAccession: SQ.cQvw4UsHHRRlogxbWCB8W-mKD4AraM9y
residueAlphabet: aa
start: 599
end: 600
sequence: V
relations:
- primaryCoding:
code: translation_of
system: http://www.sequenceontology.org
iris:
- http://www.sequenceontology.org/browser/current_release/term/translation_of
matchCharacteristic:
primaryCoding:
code: is_within
system: ga4gh-gks-term:location-match
# mappings: A list of mappings to concepts in terminologies or code systems.
# Each mapping should include a coding and a relation.
# Usually, this is intended to describe relations to concepts in other websites or systems
# For example, linking out to clinvar or dbSNP. These mappings are taken from
mappings:
- coding:
system: https://www.ncbi.nlm.nih.gov/clinvar/variation/
code: '13961'
name: NM_004333.6(BRAF):c.1799T>A (p.Val600Glu)
iris:
- https://www.ncbi.nlm.nih.gov/clinvar/variation/13961
relation: relatedMatch
- coding:
system: https://www.ncbi.nlm.nih.gov/clinvar/variation/
code: '375940'
name: NM_004333.6(BRAF):c.1798_1799delinsAG (p.Val600Arg)
iris:
- https://www.ncbi.nlm.nih.gov/clinvar/variation/375940
relation: relatedMatch
- coding:
system: https://www.ncbi.nlm.nih.gov/clinvar/variation/
code: '375941'
name: NM_004333.6(BRAF):c.1798_1799delinsAA (p.Val600Lys)
iris:
- https://www.ncbi.nlm.nih.gov/clinvar/variation/375941
relation: relatedMatch
- coding:
system: https://www.ncbi.nlm.nih.gov/clinvar/variation/
code: '40389'
name: NM_004333.6(BRAF):c.1799T>G (p.Val600Gly)
iris:
- https://www.ncbi.nlm.nih.gov/clinvar/variation/40389
relation: relatedMatch
- coding:
system: https://www.ncbi.nlm.nih.gov/clinvar/variation/
code: '44815'
name: NM_004333.6(BRAF):c.1798G>A (p.Val600Met)
iris:
- https://www.ncbi.nlm.nih.gov/clinvar/variation/44815
relation: relatedMatch
# members: A non-exhaustive list of VRS variation Constraints that satisfy the constraints of this categorical variant.
# Here, we are describing VRS alleles that satisfy BRAF V600
# The VariantNormalizer is a useful API tool to retrieve VRS Alleles based on HGVS representation
# https://normalize.cancervariants.org/variation
members:
- id: ga4gh:VA.W6xsV-aFm9yT2Bic5cFAV2j0rll6KK5R
type: Allele
name: NM_004333.6:c.1799T>A
description: VRS variation of NM_004333.6:c.1799T>A, generated with the VICC Variation Normalizer (https://github.com/cancervariants/variation-normalization).
digest: W6xsV-aFm9yT2Bic5cFAV2j0rll6KK5R
expressions:
- syntax: hgvs.c
value: NM_004333.6:c.1799T>A
location:
id: ga4gh:SL.8HBKs9fzlT3tKWlM03REjkg_0Om6Y33U
description: Coding DNA (cDNA) position 1799 of the BRAF MANE Select coding transcript (refseq:NM_004333.6), corresponding to genomic position 140753336 on chromosome 7 (refseq:NC_000007.14, GRCh38).
extensions:
- name: GRCh38 1-based, genomic position
value: chr7:140753336
description: Genomic position 140,753,336 on chromosome 7 (refseq:NC_000007.14, GRCh38).
- name: GRCh38 1-based, inclusive interval
value: chr7:140753336-140753336
description: Genomic positions 140,753,336 to 140,753,336 on chromosome 7 (refseq:NC_000007.14, GRCh38); 1-based, inclusive interval notation.
- name: GRCh38 0-based, half-open interval
value: chr7:140753335-140753337
description: Genomic positions 140,753,335 to 140,753,336 on chromosome 7 (refseq:NC_000007.14, GRCh38); 0-based, half-open interval notation.
type: SequenceLocation
digest: 8HBKs9fzlT3tKWlM03REjkg_0Om6Y33U
sequenceReference:
id: refseq:NM_004333.6
name: NM_004333.6
description: The MANE Select (GRCh38) coding transcript for BRAF.
aliases:
- ga4gh:SQ.aKMPEJgmlZXt_F6gRY5cUG3THH2n-GUa
type: SequenceReference
refgetAccession: SQ.aKMPEJgmlZXt_F6gRY5cUG3THH2n-GUa
residueAlphabet: na
start: 2024
end: 2025
sequence: T
state:
type: LiteralSequenceExpression
sequence: A
- id: ga4gh:VA.GIOeMJX8rJ-q9ZGqmFRIUOGnXQ5NARht
type: Allele
name: NM_004333.6:c.1798_1799delinsAA
description: VRS variation of NM_004333.6:c.1798_1799delinsAA, generated with the VICC Variation Normalizer (https://github.com/cancervariants/variation-normalization).
digest: GIOeMJX8rJ-q9ZGqmFRIUOGnXQ5NARht
expressions:
- syntax: hgvs.c
value: NM_004333.6:c.1798_1799delinsAA
location:
id: ga4gh:SL.SXY8ShFrBAfSvtO_sXLMQKN3Ozc5awgh
description: Coding DNA (cDNA) positions 1798 to 1799 of the BRAF MANE Select coding transcript (refseq:NM_004333.6), corresponding to genomic positions 140753336 to 140753337 on chromosome 7 (refseq:NC_000007.14, GRCh38).
extensions:
- name: GRCh38 1-based, inclusive interval
value: chr7:140753336-140753337
description: Genomic positions 140,753,336 to 140,753,337 on chromosome 7 (refseq:NC_000007.14, GRCh38); 1-based, inclusive interval notation.
- name: GRCh38 0-based, half-open interval
value: chr7:140753335-140753337
description: Genomic positions 140,753,335 to 140,753,337 on chromosome 7 (refseq:NC_000007.14, GRCh38); 0-based, half-open interval notation.
type: SequenceLocation
digest: SXY8ShFrBAfSvtO_sXLMQKN3Ozc5awgh
sequenceReference:
id: refseq:NM_004333.6
name: NM_004333.6
description: The MANE Select (GRCh38) coding transcript for BRAF.
aliases:
- ga4gh:SQ.aKMPEJgmlZXt_F6gRY5cUG3THH2n-GUa
type: SequenceReference
refgetAccession: SQ.aKMPEJgmlZXt_F6gRY5cUG3THH2n-GUa
residueAlphabet: na
start: 2023
end: 2025
sequence: GT
state:
type: LiteralSequenceExpression
sequence: AA
- id: ga4gh:VA.PEphL_4Hx5JYuJPMzgu0pRQIUcz_J9p0
type: Allele
name: NM_004333.6:c.1799T>G
description: VRS variation of NM_004333.6:c.1799T>G, generated with the VICC Variation Normalizer (https://github.com/cancervariants/variation-normalization).
digest: PEphL_4Hx5JYuJPMzgu0pRQIUcz_J9p0
expressions:
- syntax: hgvs.c
value: NM_004333.6:c.1799T>G
location:
id: ga4gh:SL.8HBKs9fzlT3tKWlM03REjkg_0Om6Y33U
description: Coding DNA (cDNA) positions 1799 of the BRAF MANE Select coding transcript (refseq:NM_004333.6), corresponding to genomic position 140753336 on chromosome 7 (refseq:NC_000007.14, GRCh38).
extensions:
- name: GRCh38 1-based, genomic position
value: chr7:140753336
description: Genomic position 140,753,336 on chromosome 7 (refseq:NC_000007.14, GRCh38).
- name: GRCh38 1-based, inclusive interval
value: chr7:140753336-140753336
description: Genomic positions 140,753,336 to 140,753,336 on chromosome 7 (refseq:NC_000007.14, GRCh38); 1-based, inclusive interval notation.
- name: GRCh38 0-based, half-open interval
value: chr7:140753335-140753336
description: Genomic positions 140,753,335 to 140,753,336 on chromosome 7 (refseq:NC_000007.14, GRCh38); 0-based, half-open interval notation.
type: SequenceLocation
digest: 8HBKs9fzlT3tKWlM03REjkg_0Om6Y33U
sequenceReference:
id: refseq:NM_004333.6
name: NM_004333.6
description: The MANE Select (GRCh38) coding transcript for BRAF.
aliases:
- ga4gh:SQ.aKMPEJgmlZXt_F6gRY5cUG3THH2n-GUa
type: SequenceReference
refgetAccession: SQ.aKMPEJgmlZXt_F6gRY5cUG3THH2n-GUa
residueAlphabet: na
start: 2024
end: 2025
sequence: T
state:
type: LiteralSequenceExpression
sequence: G
- id: ga4gh:VA.O3Wd-kD48Dl1ihRUuf4vVybLaXYKFXnk
name: NM_004333.6:c.1798G>A
description: VRS variation of NM_004333.6:c.1799T>A, generated with the VICC Variation Normalizer (https://github.com/cancervariants/variation-normalization).
digest: O3Wd-kD48Dl1ihRUuf4vVybLaXYKFXnk
expressions:
- syntax: hgvs.c
value: NM_004333.6:c.1798G>A
type: Allele
location:
id: ga4gh:SL.1ReS370wzmC9PGTn13XrnG8Ot7UAKYuw
description: Coding DNA (cDNA) position 1798 of the BRAF MANE Select coding transcript (refseq:NM_004333.6), corresponding to genomic position 140753337 on chromosome 7 (refseq:NC_000007.14, GRCh38).
extensions:
- name: GRCh38 1-based, genomic position
value: chr7:140753337
description: Genomic position 140,753,337 on chromosome 7 (refseq:NC_000007.14, GRCh38).
- name: GRCh38 1-based, inclusive interval
value: chr7:140753337-140753337
description: Genomic positions 140,753,337 to 140,753,337 on chromosome 7 (refseq:NC_000007.14, GRCh38); 1-based, inclusive interval notation.
- name: GRCh38 0-based, half-open interval
value: chr7:140753336-140753337
description: Genomic positions 140,753,336 to 140,753,337 on chromosome 7 (refseq:NC_000007.14, GRCh38); 0-based, half-open interval notation.
type: SequenceLocation
digest: 1ReS370wzmC9PGTn13XrnG8Ot7UAKYuw
sequenceReference:
id: refseq:NM_004333.6
name: NM_004333.6
description: The MANE Select (GRCh38) coding transcript for BRAF.
aliases:
- ga4gh:SQ.aKMPEJgmlZXt_F6gRY5cUG3THH2n-GUa
type: SequenceReference
refgetAccession: SQ.aKMPEJgmlZXt_F6gRY5cUG3THH2n-GUa
residueAlphabet: na
start: 2024
end: 2025
sequence: G
state:
type: LiteralSequenceExpression
sequence: A
- id: ga4gh:VA.t97D17VsbiAa2U-znA-Qfx6DVInBd-_-
type: Allele
name: NM_004333.6:c.1798_1799delinsAG
description: VRS variation of NM_004333.6:c.1799T>A, generated with the VICC Variation Normalizer (https://github.com/cancervariants/variation-normalization).
digest: t97D17VsbiAa2U-znA-Qfx6DVInBd-_-
expressions:
- syntax: hgvs.c
value: NM_004333.6:c.1798_1799delinsAG
location:
id: ga4gh:SL.SXY8ShFrBAfSvtO_sXLMQKN3Ozc5awgh
description: Coding DNA (cDNA) positions 1798 to 1799 of the BRAF MANE Select coding transcript (refseq:NM_004333.6), corresponding to genomic positions 140753336 to 140753337 on chromosome 7 (refseq:NC_000007.14, GRCh38).
extensions:
- name: GRCh38 1-based, inclusive interval
value: chr7:140753336-140753337
description: Genomic positions 140,753,336 to 140,753,337 on chromosome 7 (refseq:NC_000007.14, GRCh38); 1-based, inclusive interval notation.
- name: GRCh38 0-based, half-open interval
value: chr7:140753335-140753337
description: Genomic positions 140,753,335 to 140,753,337 on chromosome 7 (refseq:NC_000007.14, GRCh38); 0-based, half-open interval notation.
type: SequenceLocation
digest: SXY8ShFrBAfSvtO_sXLMQKN3Ozc5awgh
sequenceReference:
id: refseq:NM_004333.6
name: NM_004333.6
description: The MANE Select (GRCh38) coding transcript for BRAF.
aliases:
- ga4gh:SQ.aKMPEJgmlZXt_F6gRY5cUG3THH2n-GUa
type: SequenceReference
refgetAccession: SQ.aKMPEJgmlZXt_F6gRY5cUG3THH2n-GUa
residueAlphabet: na
start: 2023
end: 2025
sequence: GT
state:
type: LiteralSequenceExpression
sequence: AG