Submissions for variant NM_007294.4(BRCA1):c.441+18CTT[6]

dbSNP: rs147856441

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000210985	SCV000321096	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2016-09-28	reviewed by expert panel	curation	Class 1 not pathogenic based on frequency >1% in an outbred sampleset. Frequency 0.3559 (European), 0.3321 (African), 0.4006 (Admixed American/Latino), 0.3899 (East Asian), 0.5204 (South Asian), derived from 1000 genomes (2013-05-02).
Michigan Medical Genetics Laboratories, University of Michigan	RCV000210985	SCV000195881	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2014-11-03	criteria provided, single submitter	clinical testing
GeneDx	RCV000159863	SCV000209911	benign	Familial cancer of breast	2013-12-19	criteria provided, single submitter	clinical testing	The variant is found in HEREDICANCER panel(s).
GeneKor MSA	RCV000501726	SCV000693600	benign	not specified	2017-11-01	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003150101	SCV003838910	benign	Breast and/or ovarian cancer	2021-06-14	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000501726	SCV004026814	benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001353472	SCV000591269	benign	Malignant tumor of breast		no assertion criteria provided	clinical testing	The BRCA1 c.441+36_441+38delCTT variant was not identified in the literature nor was it identified in the NHLBI Exome Sequencing Project (Exome Variant Server), Exome Aggregation Consortium (ExAC) database, HGMD, LOVD, COSMIC, the ClinVar database, GeneInsight VariantWire database and the BIC database. The variant was identified in dbSNP (ID: rs147856441) and UMD (16X as a neutral variant). This variant was also identified in the 1000 Genomes Project in 1977 of 5008 chromosomes (frequency: 0.395), increasing the likelihood this could be a low frequency benign variant. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information, this variant meets our laboratory's criteria to be classified as benign.
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV000501726	SCV001906168	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000501726	SCV001927287	benign	not specified		no assertion criteria provided	clinical testing