Submissions for variant NM_007294.4(BRCA1):c.81-13C>G

dbSNP: rs56328013

Total submissions: 22

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000031282	SCV000244412	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 = 0.000301. Also class 1 based on frequency >1% in an outbred sampleset. Frequency 0.0122 (African), derived from 1000 genomes (2012-04-30).
Counsyl	RCV000031282	SCV000154032	likely benign	Breast-ovarian cancer, familial, susceptibility to, 1	2014-04-05	criteria provided, single submitter	literature only
Eurofins Ntd Llc (ga)	RCV000723932	SCV000202276	uncertain significance	not provided	2014-03-17	criteria provided, single submitter	clinical testing
GeneDx	RCV000723932	SCV000209900	likely benign	not provided	2021-06-17	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 26287763, 21523855, 22034289, 22505045, 16267036, 21673748, 17924331, 21990134, 23893897, 25556971, 30209399, 31143303)
Labcorp Genetics (formerly Invitae), Labcorp	RCV001080468	SCV000261618	benign	Hereditary breast ovarian cancer syndrome	2025-02-03	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000474249	SCV000540979	benign	Familial cancer of breast	2017-02-23	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000579728	SCV000683364	benign	Hereditary cancer-predisposing syndrome	2015-10-09	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000152870	SCV000806984	benign	not specified	2016-10-03	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000031282	SCV001287537	likely benign	Breast-ovarian cancer, familial, susceptibility to, 1	2017-04-28	criteria provided, single submitter	clinical testing	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.
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State	RCV001080468	SCV002026045	likely benign	Hereditary breast ovarian cancer syndrome	2022-04-19	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000723932	SCV002048113	benign	not provided	2024-02-23	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000579728	SCV002537912	benign	Hereditary cancer-predisposing syndrome	2020-09-01	criteria provided, single submitter	curation
Ambry Genetics	RCV000579728	SCV002679044	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: 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.
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000031282	SCV005880505	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2025-02-01	criteria provided, single submitter	clinical testing
Sharing Clinical Reports Project (SCRP)	RCV000031282	SCV000053887	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2008-07-29	no assertion criteria provided	clinical testing
Breast Cancer Information Core (BIC) (BRCA1)	RCV000031282	SCV000144221	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 1	2002-05-29	no assertion criteria provided	clinical testing
Brotman Baty Institute, University of Washington	RCV000031282	SCV001237811	not provided	Breast-ovarian cancer, familial, susceptibility to, 1		no assertion provided	in vitro
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001357880	SCV001553474	likely benign	Malignant tumor of breast		no assertion criteria provided	clinical testing	The BRCA1 c.81-13C>G variant was identified in the literature but a frequency in an affected population was not provided. The variant was determined by multiple studies, using RNA analysis and a posterior probability model, to be likely neutral (Easton 2007, Houdayer 2012, Lindor 2012). The variant was also identified in dbSNP (ID: rs56328013) as "With Likely benign, other allele", ClinVar (classified as benign by ENIGMA expert panel, Invitae, SCRP and three other submitters; as likely benign by GeneDx; and as uncertain significance by two submitters), and in LOVD 3.0 (11x). The variant was not identified in UMD-LSDB. The variant was identified in control databases in 63 of 272198 chromosomes (1 homozygous) at a frequency of 0.0002 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 54 of 23680 chromosomes (freq: 0.002, increasing the likelihood this could be a low frequency benign variant), Latino in 6 of 33822 chromosomes (freq: 0.0002), European in 1 of 124238 chromosomes (freq: 0.000008), and South Asian in 2 of 29862 chromosomes (freq: 0.00007), while the variant was not observed in the Other, Ashkenazi Jewish, East Asian, or Finnish populations. The variant occurs outside of the splicing consensus sequence and 2 of 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000152870	SCV001927764	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000152870	SCV001951651	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000152870	SCV001968834	benign	not specified		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000152870	SCV002035920	benign	not specified		no assertion criteria provided	clinical testing