ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.5468-10C>A
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_007294.4(BRCA1):c.5468-10C>A
Variation ID: 55589 Accession: VCV000055589.86
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43045812 (GRCh38) [ NCBI UCSC ] 17: 41197829 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 1, 2014 Apr 15, 2024 Jan 12, 2015 - HGVS
- ... more HGVS ... less HGVS
- Protein change
- Other names
- IVS23-10C>A
- IVS 23-10C>A
- Canonical SPDI
- NC_000017.11:43045811:G:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- functionally_normal Sequence Ontology [SO:0002219]
- The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5468-10C>A, a INTRONIC variant, produced a function score of -0.69, corresponding to a functional classification of FUNCTIONAL. 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]
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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0.00559 (T)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD), exomes 0.00120
Trans-Omics for Precision Medicine (TOPMed) 0.00425
Exome Aggregation Consortium (ExAC) 0.00141
The Genome Aggregation Database (gnomAD) 0.00464
1000 Genomes Project 0.00559
1000 Genomes Project 30x 0.00640
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00507
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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BRCA1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
12795 | 14565 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Benign (8) |
reviewed by expert panel
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Jan 12, 2015 | RCV000112663.19 | |
Benign (4) |
criteria provided, multiple submitters, no conflicts
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Feb 1, 2024 | RCV000167846.27 | |
Benign (9) |
criteria provided, multiple submitters, no conflicts
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Aug 15, 2023 | RCV000168524.36 | |
Benign (1) |
criteria provided, single submitter
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Feb 23, 2017 | RCV000463892.9 | |
Benign (3) |
criteria provided, multiple submitters, no conflicts
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May 21, 2020 | RCV000580840.12 | |
Benign (1) |
no assertion criteria provided
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- | RCV001353821.9 | |
Benign (2) |
criteria provided, multiple submitters, no conflicts
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Dec 1, 2023 | RCV001811344.22 | |
Benign (1) |
criteria provided, single submitter
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Mar 10, 2022 | RCV002496719.8 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Benign
(Jan 12, 2015)
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reviewed by expert panel
Method: curation
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Breast-ovarian cancer, familial 1
Affected status: unknown
Allele origin:
germline
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Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)
Accession: SCV000244520.1
First in ClinVar: Sep 29, 2015 Last updated: Sep 29, 2015 |
Comment:
Class 1 not pathogenic based on frequency >1% in an outbred sampleset. Frequency 0.01626 (African), derived from 1000 genomes (2012-04-30).
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Benign
(Apr 21, 2016)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
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Michigan Medical Genetics Laboratories, University of Michigan
Accession: SCV000267721.1
First in ClinVar: Sep 29, 2015 Last updated: Sep 29, 2015 |
Tissue: Blood
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Benign
(Feb 23, 2017)
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criteria provided, single submitter
Method: clinical testing
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Familial cancer of breast
(Autosomal dominant inheritance)
Affected status: no
Allele origin:
germline
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Baylor Genetics
Accession: SCV000540966.1
First in ClinVar: Apr 17, 2017 Last updated: Apr 17, 2017 |
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Benign
(Jul 19, 2017)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV000806974.1
First in ClinVar: May 03, 2018 Last updated: May 03, 2018 |
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Benign
(Jun 14, 2020)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
unknown
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Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV001469398.1
First in ClinVar: Jan 26, 2021 Last updated: Jan 26, 2021 |
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Benign
(Nov 01, 2021)
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criteria provided, single submitter
Method: research
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Hereditary breast ovarian cancer syndrome
Affected status: yes
Allele origin:
germline
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Genetics Program, Instituto Nacional de Cancer
Accession: SCV002515235.1
First in ClinVar: Nov 19, 2022 Last updated: Nov 19, 2022 |
Geographic origin: Brazil
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Benign
(May 21, 2020)
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criteria provided, single submitter
Method: curation
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Sema4, Sema4
Accession: SCV002537860.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022 |
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Benign
(Nov 18, 2014)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV002653862.1
First in ClinVar: Nov 29, 2022 Last updated: Nov 29, 2022 |
Comment:
This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA … (more)
This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
Number of individuals with the variant: 1
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Benign
(Apr 07, 2014)
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criteria provided, single submitter
Method: clinical testing
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Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000494331.2
First in ClinVar: Feb 04, 2017 Last updated: Dec 11, 2022 |
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Benign
(Jan 02, 2014)
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criteria provided, single submitter
Method: literature only
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Breast-ovarian cancer, familial 1
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000153994.2
First in ClinVar: Jun 04, 2014 Last updated: Dec 24, 2022 |
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Benign
(Aug 15, 2023)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Accession: SCV002550940.4
First in ClinVar: Jul 30, 2022 Last updated: Aug 18, 2023 |
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Benign
(Feb 01, 2024)
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criteria provided, single submitter
Method: clinical testing
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Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000077020.15
First in ClinVar: Jul 03, 2013 Last updated: Feb 20, 2024 |
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Benign
(Nov 22, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000602676.9
First in ClinVar: Aug 27, 2017 Last updated: Feb 20, 2024 |
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Benign
(Dec 01, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV004041994.5
First in ClinVar: Oct 14, 2023 Last updated: Apr 15, 2024 |
Comment:
BRCA1: BS1, BS2
Number of individuals with the variant: 2
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Benign
(Jul 08, 2015)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000228063.5
First in ClinVar: Jun 28, 2015 Last updated: Sep 22, 2018 |
Number of individuals with the variant: 6
Sex: mixed
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Benign
(Apr 19, 2022)
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criteria provided, single submitter
Method: clinical testing
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Hereditary breast ovarian cancer syndrome
Affected status: yes
Allele origin:
germline
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National Health Laboratory Service, Universitas Academic Hospital and University of the Free State
Accession: SCV002025895.2
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
Number of individuals with the variant: 55
Geographic origin: South Africa
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Benign
(Dec 06, 2014)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Color Diagnostics, LLC DBA Color Health
Accession: SCV000683320.2
First in ClinVar: Feb 19, 2018 Last updated: Dec 11, 2022 |
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Benign
(Mar 10, 2022)
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criteria provided, single submitter
Method: clinical testing
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Familial cancer of breast
Breast-ovarian cancer, familial, susceptibility to, 1 Pancreatic cancer, susceptibility to, 4 Fanconi anemia, complementation group S
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002809065.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Benign
(Jul 07, 2023)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
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KCCC/NGS Laboratory, Kuwait Cancer Control Center
Accession: SCV004016772.1
First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023 |
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Uncertain significance
(May 29, 2002)
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no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial 1
Affected status: yes
Allele origin:
germline
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Breast Cancer Information Core (BIC) (BRCA1)
Accession: SCV000145527.1
First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
Observation 1:
Number of individuals with the variant: 6
Observation 2:
Number of individuals with the variant: 1
Geographic origin: African American
Observation 3:
Number of individuals with the variant: 1
Geographic origin: Latin American, Caribbean
Observation 4:
Number of individuals with the variant: 4
Ethnicity/Population group: African American
Observation 5:
Number of individuals with the variant: 1
Ethnicity/Population group: Latin American, Caribbean
Observation 6:
Number of individuals with the variant: 1
Ethnicity/Population group: Native American, African American
Observation 7:
Number of individuals with the variant: 1
Ethnicity/Population group: Near Eastern Mid East
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Likely benign
(Jul 24, 2014)
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no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial 1
Affected status: unknown
Allele origin:
germline
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Pathway Genomics
Accession: SCV000189894.1
First in ClinVar: Oct 19, 2014 Last updated: Oct 19, 2014 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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Malignant tumor of breast
Affected status: yes
Allele origin:
unknown
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Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000591634.2 First in ClinVar: Aug 27, 2017 Last updated: Apr 13, 2021 |
Comment:
The BRCA1 c.5468-10C>A variant was identified in 3 of 4550 proband chromosomes from individuals or families with breast or ovarian cancer (frequency: 0.001); however control … (more)
The BRCA1 c.5468-10C>A variant was identified in 3 of 4550 proband chromosomes from individuals or families with breast or ovarian cancer (frequency: 0.001); however control chromosomes were not included in these studies (Borg 2010, Tommasi 2008, Uhrhammer 2008).The variant is located in the 3' splice region but does not affect the invariant -1 and -2 positions. However, positions -3 and -5 to -12 are part of the splicing consensus sequence and variants involving these positions sometimes affect splicing. One functional study did not find any effect of the variant on splicing (Houdayer 2012), and in-silico or computational prediction software (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predicts a greater than 10% difference in splicing in only 2 of 5 different programs, though this information is not predictive enough to rule out pathogenicity. The variant was also identified in HGMD, LOVD, and the BIC database (15X with unknown clinical importance), and UMD (31X as a neutral variant). In UMD the variant was identified in four samples as co-occurring a pathogenic variant (two in BRCA1 and two in BRCA2), increasing the likelihood that the variant does not have clinical importance. The variant was listed in dbSNP (ID: rs8176316) with a minor allele frequency of 0.004 (1000 Genomes Project) and an average heterozygosity of 0.007+/-0.060. Furthermore, this variant occurs at a frequency of greater than 1% in some populations of origin and is therefore classified as a polymorphism (African American alleles in the NHLBI Exome Sequencing Project (Exome Variant Server) (frequency: 0.014), HapMap-YRI (frequency: 0.018), HAPMAP-LWK (frequency: 0.017), and HAPMAP-ASW (frequency: 0.01)). In summary, based on the above information, this variant meets our laboratory's criteria to be classified as benign. (less)
Number of individuals with the variant: 3
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001906339.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001932453.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001958801.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001974514.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV002035600.1 First in ClinVar: Dec 18, 2021 Last updated: Dec 18, 2021 |
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Benign
(Mar 02, 2020)
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no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
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BRCAlab, Lund University
Accession: SCV004243909.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
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not provided
(-)
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no classification provided
Method: in vitro
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Breast-ovarian cancer, familial 1
Affected status: not applicable
Allele origin:
not applicable
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Brotman Baty Institute, University of Washington
Accession: SCV001237527.1
First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020 |
Method: saturation genome editing in haploid cells
Result:
FUNCTIONAL:-0.68844701967432
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Germline Functional Evidence
Functional
Help
The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence |
Method
Help
A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter. |
Result
Help
A brief description of the result of this method for this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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functionally_normal
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Method citation(s):
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Brotman Baty Institute, University of Washington
Accession: SCV001237527.1
|
Comment:
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5468-10C>A, a INTRONIC variant, produced a function score of -0.69, corresponding to a functional classification of FUNCTIONAL. … (more)
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5468-10C>A, a INTRONIC variant, produced a function score of -0.69, corresponding to a functional classification of FUNCTIONAL. 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. (less)
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Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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- | - | - | - | DOI: 10.3389/fgene.2022.834265 |
- | - | - | - | PMID: 16267036 |
- | - | - | - | PMID: 18645608 |
- | - | - | - | PMID: 18694767 |
- | - | - | - | PMID: 22034289 |
- | - | - | - | PMID: 22505045 |
- | - | - | - | PMID: 24729269 |
- | - | - | - | PMID: 30209399 |
- | - | - | - | PMID: 36329109 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=BRCA1 | - | - | - | - |
https://sge.gs.washington.edu/BRCA1/ | - | - | - | - |
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Text-mined citations for rs8176316 ...
HelpRecord last updated Apr 20, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.