17-61693511-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_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. C832Y) has been classified as Likely benign.
Frequency
Consequence
NM_032043.3 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Ensembl
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
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. 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. ClinVar contains an entry for this variant (Variation ID: 945582). 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). This variant is present in population databases (rs768222842, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with BRIP1-related conditions. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at