NM_007294.3(BRCA1):c.4675+1G>A AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Feb 21, 2018
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000048623.6

Allele description

NM_007294.3(BRCA1):c.4675+1G>A

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.4675+1G>A

HGVS:

NC_000017.11:g.43074330C>T
NG_005905.2:g.143654G>A
NM_007294.3:c.4675+1G>A
LRG_292t1:c.4675+1G>A
LRG_292:g.143654G>A
NC_000017.10:g.41226347C>T
U14680.1:n.4794+1G>A

Nucleotide change:

IVS15+1G>A

Links:

BRCA1-HCI: BRCA1_00127; Breast Cancer Information Core (BIC) (BRCA1): 4794+1&base_change=G to A; dbSNP: rs80358044

NCBI 1000 Genomes Browser:

rs80358044

Molecular consequence:

NM_007294.3:c.4675+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Identifiers:: MedGen: CN517202

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000210184	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (Feb 21, 2018)	germline	clinical testing	Citation Link,
SCV000296399	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest pathogenicity assessment criteria)	Pathogenic (Oct 15, 2015)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 12491499, 21990134, 18489799, 21394826, 24667779, 26467025, 26295337

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000210184

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Pathogenic
(Feb 21, 2018)

germline

clinical testing

Citation Link,

SCV000296399

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest pathogenicity assessment criteria)

Pathogenic
(Oct 15, 2015)

germline

clinical testing

PubMed (7)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Pathologic characteristics of breast parenchyma in patients with hereditary breast carcinoma, including BRCA1 and BRCA2 mutation carriers.

Adem C, Reynolds C, Soderberg CL, Slezak JM, McDonnell SK, Sebo TJ, Schaid DJ, Myers JL, Sellers TA, Hartmann LC, Jenkins RB.

Cancer. 2003 Jan 1;97(1):1-11.

PubMed [citation]

PMID:: 12491499

A review of a multifactorial probability-based model for classification of BRCA1 and BRCA2 variants of uncertain significance (VUS).

Lindor NM, Guidugli L, Wang X, Vallée MP, Monteiro AN, Tavtigian S, Goldgar DE, Couch FJ.

Hum Mutat. 2012 Jan;33(1):8-21. doi: 10.1002/humu.21627. Epub 2011 Nov 3. Review.

PubMed [citation]

PMID:: 21990134
PMCID:: PMC3242438

See all PubMed Citations (7)

Details of each submission

From GeneDx, SCV000210184.12

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

This pathogenic variant is denoted BRCA1 c.4675+1G>A or IVS14+1G>A and consists of a G>A nucleotide substitution at the +1 position of intron 14 of the BRCA1 gene. This variant is also known as IVS15+1G>A or 4794+1G>A using alternate nomenclature. The variant destroys a canonical splice 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. Functional analyses demonstrate skipping of exon 14 (exon 15 using alternate nomenclature), resulting in multiple aberrant transcripts (Machackova 2008, Steffensen 2014). In addition, BRCA1 c.4675+1G>A has been reported in association with hereditary breast and/or ovarian cancer (Adem 2003, Gutierrez Espeleta 2012, Meisel 2017). We therefore consider this variant to be pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV000296399.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Mar 31, 2019

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