NM_004333.6(BRAF):c.469G>A (p.Val157Ile) AND RASopathy

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 12, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001854118.3

Allele description

NM_004333.6(BRAF):c.469G>A (p.Val157Ile)

Gene:

BRAF:B-Raf proto-oncogene, serine/threonine kinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7q34

Genomic location:

Preferred name:

NM_004333.6(BRAF):c.469G>A (p.Val157Ile)

HGVS:

NC_000007.14:g.140834644C>T
NG_007873.3:g.95121G>A
NM_001354609.2:c.469G>A
NM_001374244.1:c.469G>A
NM_001374258.1:c.469G>A
NM_001378467.1:c.469G>A
NM_001378468.1:c.469G>A
NM_001378469.1:c.469G>A
NM_001378470.1:c.367G>A
NM_001378471.1:c.469G>A
NM_001378472.1:c.313G>A
NM_001378473.1:c.313G>A
NM_001378474.1:c.469G>A
NM_001378475.1:c.240+15467G>A
NM_004333.6:c.469G>AMANE SELECT
NP_001341538.1:p.Val157Ile
NP_001361173.1:p.Val157Ile
NP_001361187.1:p.Val157Ile
NP_001365396.1:p.Val157Ile
NP_001365397.1:p.Val157Ile
NP_001365398.1:p.Val157Ile
NP_001365399.1:p.Val123Ile
NP_001365400.1:p.Val157Ile
NP_001365401.1:p.Val105Ile
NP_001365402.1:p.Val105Ile
NP_001365403.1:p.Val157Ile
NP_004324.2:p.Val157Ile
LRG_299t1:c.469G>A
LRG_299:g.95121G>A
NC_000007.13:g.140534444C>T
NM_004333.4:c.469G>A

Protein change:

V105I

Links:

dbSNP: rs1258111302

NCBI 1000 Genomes Browser:

rs1258111302

Molecular consequence:

NM_001378475.1:c.240+15467G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001354609.2:c.469G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374244.1:c.469G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374258.1:c.469G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001378467.1:c.469G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001378468.1:c.469G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001378469.1:c.469G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001378470.1:c.367G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001378471.1:c.469G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001378472.1:c.313G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001378473.1:c.313G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001378474.1:c.469G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_004333.6:c.469G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: RASopathy
Synonyms:: rasopathies; Noonan spectrum disorder
Identifiers:: MONDO: MONDO:0021060; MedGen: C5555857

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002167547	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (May 12, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002167547

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(May 12, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV002167547.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRAF protein function. ClinVar contains an entry for this variant (Variation ID: 503529). This variant has not been reported in the literature in individuals affected with BRAF-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 157 of the BRAF protein (p.Val157Ile).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Feb 20, 2024

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