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NM_007294.3(BRCA1):c.4986+5G>A

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Interpretation:
Pathogenic/Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
8 (Most recent: Sep 9, 2021)
Last evaluated:
Jan 30, 2019
Accession:
VCV000096936.8
Variation ID:
96936
Description:
single nucleotide variant
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NM_007294.3(BRCA1):c.4986+5G>A

Allele ID
102839
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
17q21.31
Genomic location
17: 43070923 (GRCh38) GRCh38 UCSC
17: 41222940 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NM_007294.3:c.4986+5G>A
U14680.1:n.5105+5G>A
NM_007294.4:c.4986+5G>A MANE Select
... more HGVS
Protein change
-
Other names
IVS16+5G>A
Canonical SPDI
NC_000017.11:43070922:C:T
Functional consequence
functionally_abnormal [Sequence Ontology SO:0002218]
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.4986+5G>A, a SPLICE REGION variant, produced a function score of -4, corresponding to a functional classification of LOSS_OF_FUNCTION. SGE function score ranges for classification are as follows: ‘functional’, score > -0.748; ‘intermediate’, -0.748 > score > -1.328; ‘non-functional’, score < -1.328. The median synonymous SNV scored 0.0 and the median nonsense SNV scored -2.12. [submitted by Brotman Baty Institute,University of Washington]
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
Breast Cancer Information Core (BIC) (BRCA1): 5105+5&base_change=G to A
ClinGen: CA003124
dbSNP: rs397509211
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic/Likely pathogenic 2 criteria provided, multiple submitters, no conflicts Jan 30, 2019 RCV000197490.4
Pathogenic 4 criteria provided, single submitter Oct 2, 2015 RCV000083057.6
Pathogenic 1 criteria provided, single submitter Dec 1, 2013 RCV001664392.1
Likely pathogenic 1 no assertion criteria provided Aug 24, 2021 RCV001578277.2
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
BRCA1 Sufficient evidence for dosage pathogenicity No evidence available GRCh38
GRCh37
12270 12437

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely pathogenic
(Dec 21, 2017)
criteria provided, single submitter
Method: clinical testing
Hereditary breast and ovarian cancer syndrome
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000918764.1
Submitted: (Apr 24, 2019)
Evidence details
Publications
PubMed (3)
Comment:
Variant summary: The BRCA1 c.4986+5G>A variant (alternatively known as IVS16+5G>A and 5105+5G>A) involves the alteration of a conserved intronic nucleotide and is predicted to impact … (more)
Pathogenic
(Jan 30, 2019)
criteria provided, single submitter
Method: clinical testing
Hereditary breast and ovarian cancer syndrome
Allele origin: germline
Invitae
Accession: SCV000253714.4
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (5)
Comment:
This sequence change falls in intron 15 of the BRCA1 gene. It does not directly change the encoded amino acid sequence of the BRCA1 protein, … (more)
Pathogenic
(Dec 01, 2013)
criteria provided, single submitter
Method: curation
Breast-ovarian cancer, familial 1
Breast-ovarian cancer, familial 2
Hereditary breast and ovarian cancer syndrome
Allele origin: germline
Research and Development, ARUP Laboratories
Accession: SCV001877426.1
Submitted: (Sep 09, 2021)
Evidence details
Publications
PubMed (2)
Other databases
https://arup.utah.edu/database/B…
Pathogenic
(Oct 02, 2015)
criteria provided, single submitter
Method: clinical testing
Breast-ovarian cancer, familial 1
Allele origin: germline
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge
Accession: SCV000326083.3
Submitted: (Oct 28, 2016)
Evidence details
Uncertain significance
(Mar 25, 2013)
no assertion criteria provided
Method: clinical testing
Breast-ovarian cancer, familial 1
Allele origin: germline
Breast Cancer Information Core (BIC) (BRCA1)
Accession: SCV000145236.1
Submitted: (Mar 28, 2014)
Evidence details
Pathogenic
(Jan 24, 2011)
no assertion criteria provided
Method: clinical testing
Breast-ovarian cancer, familial 1
Allele origin: germline
Sharing Clinical Reports Project (SCRP)
Accession: SCV000115131.2
Submitted: (Dec 30, 2013)
Evidence details
Likely pathogenic
(Aug 24, 2021)
no assertion criteria provided
Method: clinical testing
Breast carcinoma
(Autosomal dominant inheritance)
Allele origin: germline
Medical Genetics Laboratory, Umraniye Training and Research Hospital,University of Health Sciences
Accession: SCV001797973.2
Submitted: (Aug 24, 2021)
Evidence details
Comment:
Invasive Breast Carcinoma EST= + PRO = - HER2 = - KI = 70%
not provided
(-)
no assertion provided
Method: in vitro
Breast-ovarian cancer, familial 1
Allele origin: not applicable
Brotman Baty Institute,University of Washington
Accession: SCV001243877.1
Submitted: (Nov 12, 2018)
Evidence details
Publications
PubMed (1)

Functional evidence

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Functional consequence Method Result Submitter Supporting information
functionally_abnormal
  1. saturation genome editing in haploid cells
  2. Method citation(s):
  1. LOSS_OF_FUNCTION:-4.00493656511263
Brotman Baty Institute,University of Washington
Accession: SCV001243877.1
Submitted: (Nov 12, 2018)
Evidence details
Publications
PubMed (1)
Comment:
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.4986+5G>A, a SPLICE REGION variant, produced a function score of -4, corresponding to a functional classification of … (more)

Citations for this variant

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Title Author Journal Year Link
Accurate classification of BRCA1 variants with saturation genome editing. Findlay GM Nature 2018 PMID: 30209399
Mutation Detection in Patients With Advanced Cancer by Universal Sequencing of Cancer-Related Genes in Tumor and Normal DNA vs Guideline-Based Germline Testing. Mandelker D JAMA 2017 PMID: 28873162
Comparative in vitro and in silico analyses of variants in splicing regions of BRCA1 and BRCA2 genes and characterization of novel pathogenic mutations. Colombo M PloS one 2013 PMID: 23451180
Analysis of 30 putative BRCA1 splicing mutations in hereditary breast and ovarian cancer families identifies exonic splice site mutations that escape in silico prediction. Wappenschmidt B PloS one 2012 PMID: 23239986
Intronic variants in BRCA1 and BRCA2 that affect RNA splicing can be reliably selected by splice-site prediction programs. Vreeswijk MP Human mutation 2009 PMID: 18693280
Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization. Buratti E Nucleic acids research 2007 PMID: 17576681
Statistical features of human exons and their flanking regions. Zhang MQ Human molecular genetics 1998 PMID: 9536098
https://arup.utah.edu/database/BRCA/Variants/BRCA1.php - - - -
https://sge.gs.washington.edu/BRCA1/ - - - -

Text-mined citations for rs397509211...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Sep 18, 2021