7-140734619-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP2PP3
The NM_001374258.1(BRAF):āc.2399A>Gā(p.Tyr800Cys) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,746 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_001374258.1 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BRAF | NM_004333.6 | c.2279A>G | p.Tyr760Cys | missense_variant | 18/18 | ENST00000646891.2 | |
BRAF | NM_001374258.1 | c.2399A>G | p.Tyr800Cys | missense_variant, splice_region_variant | 19/20 | ENST00000644969.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BRAF | ENST00000646891.2 | c.2279A>G | p.Tyr760Cys | missense_variant | 18/18 | NM_004333.6 | P4 | ||
BRAF | ENST00000644969.2 | c.2399A>G | p.Tyr800Cys | missense_variant, splice_region_variant | 19/20 | NM_001374258.1 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 151862Hom.: 0 Cov.: 31
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461884Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 727240
GnomAD4 genome AF: 0.00000658 AC: 1AN: 151862Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74144
ClinVar
Submissions by phenotype
RASopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 07, 2022 | This variant has not been reported in the literature in individuals affected with BRAF-related conditions. 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 expected to disrupt BRAF protein function. ClinVar contains an entry for this variant (Variation ID: 568014). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 760 of the BRAF protein (p.Tyr760Cys). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at