17-61693511-A-G
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP3_Moderate
The NM_032043.3(BRIP1):c.2494T>C(p.Cys832Arg) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000000686 in 1,457,616 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C832F) has been classified as Uncertain significance.
Frequency
Consequence
NM_032043.3 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BRIP1 | NM_032043.3 | c.2494T>C | p.Cys832Arg | missense_variant, splice_region_variant | 18/20 | ENST00000259008.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BRIP1 | ENST00000259008.7 | c.2494T>C | p.Cys832Arg | missense_variant, splice_region_variant | 18/20 | 1 | NM_032043.3 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250902Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135672
GnomAD4 exome AF: 6.86e-7 AC: 1AN: 1457616Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 725436
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Familial cancer of breast;C1836860:Fanconi anemia complementation group J Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 15, 2023 | ClinVar contains an entry for this variant (Variation ID: 945582). 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. This variant has not been reported in the literature in individuals affected with BRIP1-related conditions. This variant is present in population databases (rs768222842, gnomAD 0.003%). This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 832 of the BRIP1 protein (p.Cys832Arg). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at