17-61808744-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3
The NM_032043.3(BRIP1):āc.641G>Cā(p.Cys214Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,460,776 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Synonymous variant affecting the same amino acid position (i.e. C214C) has been classified as Likely benign.
Frequency
Consequence
NM_032043.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BRIP1 | NM_032043.3 | c.641G>C | p.Cys214Ser | missense_variant | 7/20 | ENST00000259008.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BRIP1 | ENST00000259008.7 | c.641G>C | p.Cys214Ser | missense_variant | 7/20 | 1 | NM_032043.3 | P2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000801 AC: 2AN: 249804Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135160
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1460776Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 726760
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 27, 2022 | The p.C214S variant (also known as c.641G>C), located in coding exon 6 of the BRIP1 gene, results from a G to C substitution at nucleotide position 641. The cysteine at codon 214 is replaced by serine, an amino acid with dissimilar properties. One study detected this alteration in 1/549 ovarian cancer cases and 0/1366 controls from the Netherlands and did not detect this alteration in any ovarian cancer cases or controls from either Spain or Iceland (Rafnar T et al. Nat. Genet., 2011 Oct;43:1104-7). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Apr 17, 2019 | - - |
Familial cancer of breast;C1836860:Fanconi anemia complementation group J Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 06, 2022 | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 not expected to disrupt BRIP1 protein function. ClinVar contains an entry for this variant (Variation ID: 483206). This variant has not been reported in the literature in individuals affected with BRIP1-related conditions. This variant is present in population databases (rs779409059, gnomAD 0.002%). This sequence change replaces cysteine, which is neutral and slightly polar, with serine, which is neutral and polar, at codon 214 of the BRIP1 protein (p.Cys214Ser). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at