ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.135-18T>G (rs80358085)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000167792 SCV000075446 uncertain significance Hereditary breast and ovarian cancer syndrome 2017-11-06 criteria provided, single submitter clinical testing This sequence change falls in intron 3 of the BRCA1 gene. It does not directly change the encoded amino acid sequence of the BRCA1 protein. This variant is present in population databases (rs80358085, ExAC 0.002%). This variant has been reported in an individual with a personal and family history of breast cancer (PMID: 23239986). This variant is also known as IVS4-18T>G in the literature. ClinVar contains an entry for this variant (Variation ID: 54214). Experimental studies have shown that this variant modestly increases skipping of exon 4 (also known as exon 5), but exon 4 skipping has also been observed in the wild-type controls at a low level (PMID: 23239986). 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 RCV000047433 SCV000210064 uncertain significance not provided 2017-10-13 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.135-18T>G or IVS3-18T>G and consists of a T>G nucleotide substitution at the -18 position of intron 3 of the BRCA1 gene. This variant, historically denoted as IVS4-18T>G using alternate nomenclature, has been observed in at least one individual with a personal and/or family history of breast and/or ovarian cancer and was found to partially affect splicing by an in vitro functional study (Wappenschmidt 2012). At least one splicing model suggests that this variant may weaken the natural splice acceptor site of intron 3. BRCA1 IVS3-18T>G was not observed at a significant allele frequency in large population cohorts (Lek 2016). The thymine (T) nucleotide that is altered is not conserved. Based on currently available evidence, it is unclear whether BRCA1 c.135-18T>G is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Counsyl RCV000111856 SCV000488022 uncertain significance Breast-ovarian cancer, familial 1 2015-12-16 criteria provided, single submitter clinical testing
Color RCV000776482 SCV000912059 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-03 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000111856 SCV000144427 uncertain significance Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing
Hereditary Cancer Genetics group,Vall d'Hebron Institute of Oncology RCV000167792 SCV000916380 uncertain significance Hereditary breast and ovarian cancer syndrome 2019-03-01 no assertion criteria provided research

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