ClinVar Miner

Submissions for variant NM_032043.3(BRIP1):c.380-5A>G

gnomAD frequency: 0.00019  dbSNP: rs587782131
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 9
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130674 SCV000185560 uncertain significance Hereditary cancer-predisposing syndrome 2023-06-05 criteria provided, single submitter clinical testing The c.380-5A>G intronic variant results from an A to G substitution 5 nucleotides upstream from coding exon 4 in the BRIP1 gene. This nucleotide position is not well conserved in available vertebrate species. In silico splice site analysis for this alteration is inconclusive and direct evidence is insufficient at this time (Ambry internal data). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV000547580 SCV000633692 likely benign Familial cancer of breast; Fanconi anemia complementation group J 2023-11-27 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000547580 SCV000895118 uncertain significance Familial cancer of breast; Fanconi anemia complementation group J 2018-10-31 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000130674 SCV000903771 likely benign Hereditary cancer-predisposing syndrome 2015-07-27 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000985642 SCV001134030 uncertain significance not provided 2019-03-07 criteria provided, single submitter clinical testing
Mendelics RCV000990037 SCV001140801 uncertain significance Familial cancer of breast 2019-05-28 criteria provided, single submitter clinical testing
GeneDx RCV000985642 SCV001822906 uncertain significance not provided 2020-01-08 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In-silico analysis, which includes splice predictors and evolutionary conservation, is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV000990037 SCV003928152 uncertain significance Familial cancer of breast 2023-04-14 criteria provided, single submitter clinical testing The BRIP1 c.380-5A>G intronic change results in an A to G substitution at the -5 position of intron 4 of the BRIP1 gene. Algorithms that predict the impact of sequence changes on splicing are inconclusive. This variant has a maximum subpopulation frequency of 0.038% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). To our knowledge, this variant has not been reported in individuals with hereditary breast and ovarian cancer syndrome or Fanconi anemia. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.
PreventionGenetics, part of Exact Sciences RCV004532564 SCV004115570 uncertain significance BRIP1-related disorder 2023-01-23 criteria provided, single submitter clinical testing The BRIP1 c.380-5A>G variant is predicted to interfere with splicing. To our knowledge, this variant has not been reported in the literature. It is reported in 0.038% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/17-59926622-T-C), which is higher than expected for a primary casue of disease. This variant is classified as a VUS and likely benign by submitters to ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/141947/). Although we suspect that this variant may be benign, at this time, the clinical significance is uncertain due to the absence of conclusive functional and genetic evidence.

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.