Submissions for variant NM_007294.4(BRCA1):c.4987-20A>G

gnomAD frequency: 0.00252  dbSNP: rs80358035

Total submissions: 21

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000077152	SCV000244376	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2015-08-10	reviewed by expert panel	curation	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 = 0.000000197
Counsyl	RCV000077152	SCV000220302	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2014-05-10	criteria provided, single submitter	literature only
Eurofins Ntd Llc (ga)	RCV000175068	SCV000226496	benign	not specified	2014-08-06	criteria provided, single submitter	clinical testing
Invitae	RCV000197931	SCV000252818	benign	Hereditary breast ovarian cancer syndrome	2024-02-01	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000197931	SCV000494368	benign	Hereditary breast ovarian cancer syndrome	2014-04-17	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000175068	SCV000538433	benign	not specified	2016-10-20	criteria provided, single submitter	clinical testing	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency; ClinVar: Classified as benign by ENIGMA expert panel (8/10/15)
Baylor Genetics	RCV000468319	SCV000540978	benign	Familial cancer of breast	2017-02-23	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000077152	SCV000575717	likely benign	Breast-ovarian cancer, familial, susceptibility to, 1	2015-08-07	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000579497	SCV000683232	benign	Hereditary cancer-predisposing syndrome	2015-06-17	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000175068	SCV000806965	benign	not specified	2017-09-29	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001811353	SCV001159430	benign	not provided	2021-08-16	criteria provided, single submitter	clinical testing
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State	RCV000197931	SCV002025920	benign	Hereditary breast ovarian cancer syndrome	2022-04-19	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000175068	SCV002550960	benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000579497	SCV002642213	benign	Hereditary cancer-predisposing syndrome	2014-11-18	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: 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.
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000077152	SCV004016761	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2023-07-07	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003492431	SCV004240273	likely benign	Breast and/or ovarian cancer	2022-07-12	criteria provided, single submitter	clinical testing
Sharing Clinical Reports Project (SCRP)	RCV000077152	SCV000108949	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2012-05-01	no assertion criteria provided	clinical testing
Breast Cancer Information Core (BIC) (BRCA1)	RCV000077152	SCV000145243	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 1	1999-12-30	no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000175068	SCV000591553	benign	not specified		no assertion criteria provided	clinical testing	The BRCA1 c.4987-20A>G variant was identified in ClinVar (Benign, reviewed by expert panel. Classified as benign by: ENIGMA, Integrated Genetics, LMM Partners HealthCare, Baylor, EGL, ARUP Laboratories, Invitae, Counsyl, Color, Prevention Genetics, SCRP. Classified as likely benign by COGR, Fulgent. VUS by BIC). The variant was identified in dbSNP (rs80358035). The variant was identified in control databases in 226 of 282334 chromosomes (2 homozygous) at a frequency of 0.0008005, and was observed at the highest frequency in the African population in 209 of 24924 chromosomes (freq: 0.008385) (Genome Aggregation Database March 6, 2019, v2.1.1). The variant occurs outside of the splicing consensus sequence, and in silico or computational prediction software programs (Splice AI exome) do not predict a deleterious effect on splicing. In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000175068	SCV001929708	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000175068	SCV001976291	benign	not specified		no assertion criteria provided	clinical testing