Submissions for variant NM_007294.4(BRCA1):c.-20+11C>T

gnomAD frequency: 0.00042  dbSNP: rs273898672

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000123934	SCV000167321	benign	not specified	2014-01-23	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Counsyl	RCV000111489	SCV000489588	likely benign	Breast-ovarian cancer, familial, susceptibility to, 1	2016-10-25	criteria provided, single submitter	clinical testing
Invitae	RCV000860869	SCV001001040	benign	Hereditary breast ovarian cancer syndrome	2024-02-01	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV002258793	SCV002538079	likely benign	Hereditary cancer-predisposing syndrome	2022-02-28	criteria provided, single submitter	curation
PreventionGenetics, part of Exact Sciences	RCV003894945	SCV004714555	likely benign	BRCA1-related condition	2022-12-15	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Breast Cancer Information Core (BIC) (BRCA1)	RCV000111489	SCV000143931	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 1	1999-06-22	no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001353442	SCV000591226	likely benign	Malignant tumor of breast		no assertion criteria provided	clinical testing	The c.-20+11C>T variant was not identified in the literature. It was reported in the dbSNP database (ID: rs273898672) but no frequency data was provided and so the variant’s frequency in the general population is not known. This variant occurs upstream of the start site and +11bp away from the exon/intron junction of non-coding exon 1 of the BRCA1 gene. The variant is located in the 5' splice region (or near the 3' splice site of exon 1) but does not affect the invariant +1 and +2 positions. This variant occurs outside of the splicing consensus sequence; +3 to +6 are part of the splicing consensus sequence and variants involving these positions sometimes affect splicing. Furthermore, in-silico or computational prediction software (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a significantly different splicing affect, increasing the likelihood this variant may not have clinical significance; although this information is not predictive enough to out 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 predicted benign.
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV001689635	SCV001906446	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001689635	SCV001952085	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001689635	SCV001978335	likely benign	not provided		no assertion criteria provided	clinical testing
BRCAlab, Lund University	RCV000111489	SCV004244212	likely benign	Breast-ovarian cancer, familial, susceptibility to, 1	2020-03-02	no assertion criteria provided	clinical testing