Submissions for variant NM_007294.4(BRCA1):c.4987-5T>C

dbSNP: rs397509214

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000258194	SCV000326098	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-02	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000797612	SCV000937179	likely pathogenic	Hereditary breast ovarian cancer syndrome	2024-04-01	criteria provided, single submitter	clinical testing	This sequence change falls in intron 15 of the BRCA1 gene. It does not directly change the encoded amino acid sequence of the BRCA1 protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with hereditary breast and/or ovarian cancer (PMID: 29446198, 30078507, 35918668). ClinVar contains an entry for this variant (Variation ID: 267568). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this variant affects BRCA1 function (PMID: 30209399). Studies have shown that this variant results in skipping of exon 16 and introduces a premature termination codon (Invitae). The resulting mRNA is expected to undergo nonsense-mediated decay. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State	RCV000797612	SCV002025919	likely pathogenic	Hereditary breast ovarian cancer syndrome	2021-11-16	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV000258194	SCV005407503	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 1	2024-09-04	criteria provided, single submitter	clinical testing	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.
Juno Genomics, Hangzhou Juno Genomics, Inc	RCV004796145	SCV005415812	likely pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1; Pancreatic cancer, susceptibility to, 4; Fanconi anemia, complementation group S		criteria provided, single submitter	clinical testing	PM2_Supporting+PS4_Supporting+PS3
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496749	SCV000587442	uncertain significance	not specified	2014-01-31	no assertion criteria provided	research
Brotman Baty Institute, University of Washington	RCV000258194	SCV001243886	not provided	Breast-ovarian cancer, familial, susceptibility to, 1		no assertion provided	in vitro
Center for Precision Medicine, Meizhou People's Hospital	RCV002250609	SCV002520791	pathogenic	Familial cancer of breast		no assertion criteria provided	literature only