NM_007294.3(BRCA1):c.5194-18G>T AND not specified

Clinical significance:Likely benign (Last evaluated: Jul 18, 2021)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000781030.2

Allele description [Variation Report for NM_007294.3(BRCA1):c.5194-18G>T]

NM_007294.3(BRCA1):c.5194-18G>T

Gene:
BRCA1:BRCA1 DNA repair associated [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17q21.31
Genomic location:
Preferred name:
NM_007294.3(BRCA1):c.5194-18G>T
Other names:
IVS19-18G>T
HGVS:
  • NC_000017.11:g.43057153C>A
  • NG_005905.2:g.160831G>T
  • NM_007294.3:c.5194-18G>T
  • NM_007297.4:c.5053-18G>T
  • NM_007298.3:c.1882-18G>T
  • NM_007299.4:c.1882-18G>T
  • NM_007300.4:c.5257-18G>T
  • LRG_292t1:c.5194-18G>T
  • LRG_292:g.160831G>T
  • NC_000017.10:g.41209170C>A
  • U14680.1:n.5313-18G>T
Links:
Breast Cancer Information Core (BIC) (BRCA1): 5313-18&base_change=G to T; dbSNP: rs80358090
NCBI 1000 Genomes Browser:
rs80358090
Molecular consequence:
  • NM_007294.3:c.5194-18G>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_007297.4:c.5053-18G>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_007298.3:c.1882-18G>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_007299.4:c.1882-18G>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_007300.4:c.5257-18G>T - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000918795Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Likely benign
(Jul 18, 2021)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

High prevalence of BRCA1 and BRCA2 mutations in unselected Nigerian breast cancer patients.

Fackenthal JD, Zhang J, Zhang B, Zheng Y, Hagos F, Burrill DR, Niu Q, Huo D, Sveen WE, Ogundiran T, Adebamowo C, Odetunde A, Falusi AG, Olopade OI.

Int J Cancer. 2012 Sep 1;131(5):1114-23. doi: 10.1002/ijc.27326. Epub 2012 Jan 27.

PubMed [citation]
PMID:
22034289

Contribution of bioinformatics predictions and functional splicing assays to the interpretation of unclassified variants of the BRCA genes.

Théry JC, Krieger S, Gaildrat P, Révillion F, Buisine MP, Killian A, Duponchel C, Rousselin A, Vaur D, Peyrat JP, Berthet P, Frébourg T, Martins A, Hardouin A, Tosi M.

Eur J Hum Genet. 2011 Oct;19(10):1052-8. doi: 10.1038/ejhg.2011.100. Epub 2011 Jun 15.

PubMed [citation]
PMID:
21673748
PMCID:
PMC3190263
See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000918795.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

Variant summary: BRCA1 c.5194-18G>T alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. One functional study did not find splicing defects (Thery_2011). The variant allele was found at a frequency of 4.8e-05 in 251484 control chromosomes, predominantly at a frequency of 0.00068 within the African or African-American subpopulation in the gnomAD database. This frequency is not significantly higher than expected for a pathogenic variant in BRCA1 causing Hereditary Breast And Ovarian Cancer Syndrome (4.8e-05 vs 0.001), allowing no conclusion about variant significance. c.5194-18G>T has been reported in the literature as a VUS in individuals affected with Hereditary Breast And Ovarian Cancer (example, Judkins_2005, Fackenthal_2012). These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. To our knowledge, no other experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Aug 7, 2021

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