rs786201632
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The ENST00000259008.7(BRIP1):āc.2885T>Cā(p.Ile962Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,612,364 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I962V) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000259008.7 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
BRIP1 | NM_032043.3 | c.2885T>C | p.Ile962Thr | missense_variant | 19/20 | ENST00000259008.7 | NP_114432.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
BRIP1 | ENST00000259008.7 | c.2885T>C | p.Ile962Thr | missense_variant | 19/20 | 1 | NM_032043.3 | ENSP00000259008 | P2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152220Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250396Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135452
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1460144Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 726476
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152220Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74370
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | May 08, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 26, 2024 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Nov 25, 2022 | Variant summary: BRIP1 c.2885T>C (p.Ile962Thr) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 250396 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.2885T>C has been reported in the literature citing the ClinVar database classification as a VUS (as of May-2019) among a discovery cohort of individuals affected with early onset breast cancer (example, Moyer_2020). These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (likely benign, n=1; VUS, n=3). Based on the evidence outlined above, the variant was classified as uncertain significance. - |
BRIP1-related disorder Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 05, 2024 | The BRIP1 c.2885T>C variant is predicted to result in the amino acid substitution p.Ile962Thr. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0016% of alleles in individuals of European (Non-Finnish) descent in gnomAD. This variant is interpreted as a variant of uncertain significance by majority of the submitters in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/184706/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Ovarian neoplasm;C1836860:Fanconi anemia complementation group J Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Jul 14, 2017 | - - |
Familial cancer of breast Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Myriad Genetics, Inc. | Feb 28, 2023 | This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk. - |
Familial cancer of breast;C1836860:Fanconi anemia complementation group J Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 24, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at