rs41286300
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PP3_ModerateBP6_Very_Strong
The NM_007294.4(BRCA1):c.2596C>T(p.Arg866Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000194 in 1,613,668 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 Benign (★★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R866H) has been classified as Benign.
Frequency
Consequence
NM_007294.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BRCA1 | NM_007294.4 | c.2596C>T | p.Arg866Cys | missense_variant | 10/23 | ENST00000357654.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BRCA1 | ENST00000357654.9 | c.2596C>T | p.Arg866Cys | missense_variant | 10/23 | 1 | NM_007294.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000118 AC: 18AN: 152144Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000147 AC: 37AN: 251070Hom.: 0 AF XY: 0.000169 AC XY: 23AN XY: 135710
GnomAD4 exome AF: 0.000202 AC: 295AN: 1461406Hom.: 0 Cov.: 43 AF XY: 0.000193 AC XY: 140AN XY: 727014
GnomAD4 genome ? AF: 0.000118 AC: 18AN: 152262Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74446
ClinVar
Submissions by phenotype
Breast-ovarian cancer, familial, susceptibility to, 1 Benign:8
Likely benign, criteria provided, single submitter | literature only | Counsyl | Sep 26, 2014 | - - |
Benign, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | Sep 21, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | Oct 09, 2014 | - - |
Benign, reviewed by expert panel | curation | Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) | Aug 10, 2015 | IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 1 based on posterior probability = 0.0000000000000163 - |
Benign, no assertion criteria provided | clinical testing | Breast Cancer Information Core (BIC) (BRCA1) | May 29, 2002 | - - |
Benign, no assertion criteria provided | clinical testing | Sharing Clinical Reports Project (SCRP) | Aug 21, 2008 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | May 01, 2018 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
not specified Benign:7Other:1
Benign, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital | Aug 15, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jan 05, 2022 | proposed classification - variant undergoing re-assessment, contact laboratory - |
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Sep 04, 2014 | - - |
Benign, no assertion criteria provided | clinical testing | Department of Pathology and Laboratory Medicine, Sinai Health System | - | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Benign, no assertion criteria provided | research | Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto | Jan 31, 2014 | - - |
not provided Benign:4
Benign, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Apr 25, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Jun 16, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 14, 2017 | - - |
Likely benign, no assertion criteria provided | research | Biesecker Lab/Clinical Genomics Section, National Institutes of Health | Jul 13, 2012 | - - |
Hereditary cancer-predisposing syndrome Benign:3
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 18, 2014 | This alteration is classified as 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. - |
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Apr 20, 2015 | - - |
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | May 27, 2021 | - - |
Hereditary breast ovarian cancer syndrome Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 26, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C. | Feb 14, 2024 | - - |
Breast and/or ovarian cancer Pathogenic:1
Likely pathogenic, no assertion criteria provided | clinical testing | Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research | - | - - |
Familial cancer of breast;C2676676:Breast-ovarian cancer, familial, susceptibility to, 1;C3280442:Pancreatic cancer, susceptibility to, 4;C4554406:Fanconi anemia, complementation group S Benign:1
Benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jan 24, 2022 | - - |
Familial cancer of breast Benign:1
Benign, criteria provided, single submitter | clinical testing | Baylor Genetics | Feb 23, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at