NM_007294.4(BRCA1):c.5074+1G>T AND not provided

Clinical significance:Pathogenic (Last evaluated: Aug 2, 2016)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000482341.1

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)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000568399GeneDxcriteria provided, single submitter
Pathogenic
(Aug 2, 2016)
germlineclinical testing

Citation Link

Summary from all submissions

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

Details of each submission

From GeneDx, SCV000568399.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

This variant is denoted BRCA1 c.5074+1G>T or IVS16+1G>T and consists of a G>T nucleotide substitution at the +1 position of intron 16 of the BRCA1 gene. Using alternate nomenclature, this variant has previously been published as BRCA1 5193+1G>T and IVS17+1G>T. This variant destroys a canonical splice donor site and is predicted to cause abnormal gene splicing, leading to either an abnormal message that is subject to nonsense-mediated mRNA decay or to an abnormal protein product. This variant has been reported in multiple individuals with a personal and/or family history consistent with Hereditary Breast and Ovarian Cancer (Choi 2004, Kang 2015, Gonzalez-Rivera 2016, Seifert 2016). Brose et al. (2004) performed RT-PCR studies that revealed that this variant produces a truncated protein product. In addition, Steffensen et. al. (2014) used a mingene assay to further evaluate the splicing defect caused by this variant and two aberrant transcripts were observed, both of which are expected to result in a truncated protein product. Based on the current evidence, we consider this variant to be pathogenic.

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

Last Updated: May 14, 2021

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