ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.4485-1G>T (rs80358189)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000236333 SCV000294084 pathogenic not provided 2016-03-14 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.4485-1G>T or IVS13-1G>T and consists of a G>T nucleotide substitution at the -1 position of intron 13 of the BRCA1 gene. Using alternate nomenclature, this variant would be defined as BRCA1 4604-1G>T. This variant destroys a canonical splice acceptor site and is predicted to cause abnormal gene splicing, leading to either an abnormal message that is subject to nonsense-mediated mRNA decay or to an abnormal protein product. BRCA1 c.4485-1G>T has been reported in a patient with high grade serous ovarian cancer and RT-PCR studies revealed novel transcripts in association with this variant resulting in a truncated protein (Fleury 2015). Based on the current evidence, we consider this variant to be pathogenic.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000258158 SCV000325986 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000506333 SCV000605762 pathogenic Hereditary breast and ovarian cancer syndrome 2017-01-27 criteria provided, single submitter clinical testing The c.4485-1G>T variant in BRCA1 has been reported in 1 French Canadian individu al with BRCA1-associated cancer (Fleury 2015). It was absent from large populati on studies. This variant occurs in the invariant region (+/- 1,2) of the splice consensus sequence and is predicted to cause altered splicing leading to an abno rmal or absent protein. Consistent with this prediction, in vitro functional stu dies demonstrate altered splicing and no appreciable protein expression in cells that harbor this variant in the homozygous state (Fleury 2015). In summary, the c.4485-1G>T variant meets criteria to be classified as pathogenic for hereditar y breast and ovarian cancer (HBOC) in an autosomal dominant manner based upon it s predicted impact to the protein and functional studies.
GeneKor MSA RCV000236333 SCV000693537 pathogenic not provided 2017-11-01 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.