rs397516907
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1
This summary comes from the ClinGen Evidence Repository: The filtering allele frequency of the c.968C>T (p.Ser323Leu) variant in the BRAF gene is 0.06% for South Asian chromosomes by the Exome Aggregation Consortium (17/16512 with 95% CI), which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen RASopathy Expert panel for autosomal dominant RASopathy variants (BA1). LINK:https://erepo.genome.network/evrepo/ui/classification/CA135149/MONDO:0021060/004
Frequency
Consequence
NM_001374258.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BRAF | NM_001374258.1 | c.968C>T | p.Ser323Leu | missense_variant | 7/20 | ENST00000644969.2 | |
BRAF | NM_004333.6 | c.968C>T | p.Ser323Leu | missense_variant | 7/18 | ENST00000646891.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BRAF | ENST00000644969.2 | c.968C>T | p.Ser323Leu | missense_variant | 7/20 | NM_001374258.1 | |||
BRAF | ENST00000646891.2 | c.968C>T | p.Ser323Leu | missense_variant | 7/18 | NM_004333.6 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152158Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000123 AC: 31AN: 251464Hom.: 0 AF XY: 0.000140 AC XY: 19AN XY: 135900
GnomAD4 exome AF: 0.0000752 AC: 110AN: 1461834Hom.: 0 Cov.: 31 AF XY: 0.0000963 AC XY: 70AN XY: 727216
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152276Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74454
ClinVar
Submissions by phenotype
RASopathy Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Aug 05, 2023 | - - |
Benign, reviewed by expert panel | curation | ClinGen RASopathy Variant Curation Expert Panel | Apr 03, 2017 | The filtering allele frequency of the c.968C>T (p.Ser323Leu) variant in the BRAF gene is 0.06% for South Asian chromosomes by the Exome Aggregation Consortium (17/16512 with 95% CI), which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen RASopathy Expert panel for autosomal dominant RASopathy variants (BA1). - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 18, 2012 | Variant classified as Uncertain Significance - Favor Benign. The Ser323Leu varia nt has not been reported in the literature nor previously identified by our labo ratory. Serine (Ser) at this position is conserved across mammals but not into lower species and computational analyses (biochemical amino acid properties, Pol yPhen2, SIFT, AlignGVGD) do not provide strong support for or against pathogenic ity. In the absence of additional information, the clinical significance of thi s variant cannot be determined at this time. - |
BRAF-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 05, 2021 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 28, 2019 | - - |
Noonan syndrome and Noonan-related syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Aug 20, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at