ClinVar Miner

Submissions for variant NM_004333.6(BRAF):c.1150A>G (p.Arg384Gly) (rs545495379)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen RASopathy Variant Curation Expert Panel RCV000521582 SCV000616459 benign Rasopathy 2017-04-18 reviewed by expert panel curation The filtering allele frequency of the c.1150A>G (p.Arg384Gly) variant in the BRAF gene is 0.116% (16/8646) of East Asian chromosomes by the Exome Aggregation Consortium, which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen RASopathy Expert Panel (BA1; PMID:29493581)
Invitae RCV000521582 SCV000659069 likely benign Rasopathy 2020-10-26 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001192587 SCV001360820 benign not specified 2019-12-24 criteria provided, single submitter clinical testing Variant summary: BRAF c.1150A>G (p.Arg384Gly) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00018 in 251312 control chromosomes, exclusively reported within the East Asian subpopulation at a frequency of 0.0025, in the gnomAD database. The observed variant frequency within East Asian control individuals is approximately 1000-fold of the estimated maximal allele frequency expected for a pathogenic variant in BRAF causing Noonan Syndrome and Related Conditions phenotype (2.5e-06), strongly suggesting that the variant is a benign polymorphism. c.1150A>G has been reported in the literature in a fetus with abnormal ultrasound findings (suspected of Noonan Syndrome) and in individuals with various cancer phenotypes (Croonen_2013, Zhang_2015, Griffith_2018), however, without strong evidence for causality. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two submitters, including an expert panel (ClinGen RASopathy Variant Curation Expert Panel), have provided clinical-significance assessments for this variant in ClinVar after 2014, and classified the variant as likely benign / benign (expert panel). Based on the evidence outlined above, the variant was classified as benign.

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