ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.593+4del

dbSNP: rs1555594036
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000637321 SCV000758772 uncertain significance Hereditary breast ovarian cancer syndrome 2023-02-01 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 531202). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This sequence change falls in intron 8 of the BRCA1 gene. It does not directly change the encoded amino acid sequence of the BRCA1 protein. It affects a nucleotide within the consensus splice site. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV001766360 SCV002001007 uncertain significance not provided 2020-05-01 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed in large population cohorts (Lek 2016); In silico analysis supports a deleterious effect on splicing; Also known as 712+4delG
Ambry Genetics RCV002358790 SCV002653947 uncertain significance Hereditary cancer-predisposing syndrome 2024-02-27 criteria provided, single submitter clinical testing The c.593+4delA intronic variant, located in intron 7 of the BRCA1 gene, results from a deletion of one nucleotide within intron 7 of the BRCA1 gene. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site; however, this alteration occurs at a splice junction that is located at a naturally occurring, alternatively spliced exon and, thus, the effects of abnormal splicing cannot be predicted (Ambry internal data; Colombo M et al. Hum. Mol. Genet., 2014 Jul;23:3666-80). Based on the available evidence, the clinical significance of this alteration remains unclear.
Baylor Genetics RCV003459523 SCV004215064 likely pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2023-11-27 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV005019057 SCV005647188 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 1; Pancreatic cancer, susceptibility to, 4; Fanconi anemia, complementation group S 2024-02-15 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.