ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.4484+1del (rs397509181)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000258317 SCV001161637 pathogenic Breast-ovarian cancer, familial 1 2019-06-18 reviewed by expert panel curation IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 5 based on posterior probability = 0.996657
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000258317 SCV000325973 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
GeneKor MSA RCV000585723 SCV000693535 pathogenic Hereditary breast and ovarian cancer syndrome 2020-01-01 criteria provided, single submitter clinical testing This variant is a single base pair deletion in the first base of intron 13 of the BRCA1 gene. This position is conserved in the human and other genomes and might be involved in mRNA processing. Therefore, this variant is expected to disrupt RNA splicing and results in an absent or disrupted protein product. Truncating variants in BRCA1 are known to be pathogenic. This variant has been reported in the literature in Turkish breast/ovarian families (PMID: 10952777). The mutation database ClinVar contains entries for this variant (Variation ID: 55211).
Invitae RCV000585723 SCV001574480 likely pathogenic Hereditary breast and ovarian cancer syndrome 2019-11-26 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 13 of the BRCA1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual with a personal and family history of breast and/or ovarian cancer (PMID: 10952777). This variant is also known as IVS-14+1delG in the literature. ClinVar contains an entry for this variant (Variation ID: 55211). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). 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.

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