NM_007294.4(BRCA1):c.5074+1G>T AND Hereditary breast and ovarian cancer syndrome

Clinical significance:Pathogenic (Last evaluated: Feb 27, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000496776.2

Allele description [Variation Report for NM_007294.4(BRCA1):c.5074+1G>T]

NM_007294.4(BRCA1):c.5074+1G>T

Gene:
BRCA1:BRCA1 DNA repair associated [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17q21.31
Genomic location:
Preferred name:
NM_007294.4(BRCA1):c.5074+1G>T
HGVS:
  • NC_000017.11:g.43067607C>A
  • NG_005905.2:g.150377G>T
  • NM_007294.3:c.5074+1G>T
  • NM_007294.4:c.5074+1G>TMANE SELECT
  • NM_007297.4:c.4933+1G>T
  • NM_007298.3:c.1762+1G>T
  • NM_007299.4:c.1762+1G>T
  • NM_007300.4:c.5137+1G>T
  • LRG_292t1:c.5074+1G>T
  • LRG_292:g.150377G>T
  • NC_000017.10:g.41219624C>A
  • U14680.1:n.5193+1G>T
Nucleotide change:
IVS17+1G>T
Links:
Breast Cancer Information Core (BIC) (BRCA1): 5193+1&base_change=G to T; dbSNP: rs80358053
NCBI 1000 Genomes Browser:
rs80358053
Molecular consequence:
  • NM_007294.3:c.5074+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_007294.4:c.5074+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_007297.4:c.4933+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_007298.3:c.1762+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_007299.4:c.1762+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_007300.4:c.5137+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
Functional consequence:
functionally_abnormal [Sequence Ontology: SO:0002218] - Comment(s)

Condition(s)

Name:
Hereditary breast and ovarian cancer syndrome (HBOC)
Synonyms:
Hereditary breast and ovarian cancer; Hereditary breast and ovarian cancer syndrome (HBOC)
Identifiers:
MONDO: MONDO:0003582; MeSH: D061325; MedGen: C0677776; Orphanet: 145; OMIM: PS604370

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000587451Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto - The Canadian Open Genetics Repository (COGR)no assertion criteria providedPathogenic
(Jan 31, 2014)
germlineresearch

SCV001585897Invitaecriteria provided, single submitter
Pathogenic
(Feb 27, 2020)
germlineclinical testing

PubMed (9)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Incidence of BRCA1 and BRCA2 mutations in young Korean breast cancer patients.

Choi DH, Lee MH, Bale AE, Carter D, Haffty BG.

J Clin Oncol. 2004 May 1;22(9):1638-45.

PubMed [citation]
PMID:
15117986

BRCA1/BRCA2 gene mutations/SNPs and BRCA1 haplotypes in early-onset breast cancer patients of Indian ethnicity.

Juwle A, Saranath D.

Med Oncol. 2012 Dec;29(5):3272-81. doi: 10.1007/s12032-012-0294-9. Epub 2012 Jul 3.

PubMed [citation]
PMID:
22752604
See all PubMed Citations (9)

Details of each submission

From Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto - The Canadian Open Genetics Repository (COGR), SCV000587451.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedresearchnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV001585897.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (9)

Description

This sequence change affects a donor splice site in intron 16 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 reported in individuals with breast and/or ovarian cancer (PMID: 15117986, 22752604, 29446198, 30078507). This variant is also known as IVS17+1G>T in the literature. ClinVar contains an entry for this variant (Variation ID: 37630). Experimental studies have shown that this variant disrupts mRNA splicing (PMID: 15345110, 30209399). 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). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: May 14, 2021

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