Variant summary: The c.4186-10G>A in BRCA1 gene is an intronic change that involves a non-conserved nucleotide. 4/5 programs in Alamut predict that this variant does not affect normal splicing, however no functional studies supporting this notion were published at the time of evaluation. The variant is present in the control population dataset of ExAC, mainly in individuals of East Asian descent at frequency of 0.17%, including one homozygous occurrence. The observed frequency exceeds the maximum expected allele frequency for a pathogenic BRCA1 variant, suggesting that it is a polymorphism. The fact that c.4186-10G>A has been reported to co-occur with two different deleterious mutation in BRCA1 gene (c.3700_3704delGTAAA and c.3759_3760delTA) suggests a non-disease causing nature of this variant. In addition, the variant has been reported as Polymorphismin published reports (Soumittra, 2009). Taken together, this variant has been classified as Benign.
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.4186-10G>A
Germline
Classification
Help
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.
(15)
Help
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.
Conflicting classifications of pathogenicity
Uncertain significance(1); Benign(5); Likely benign(6)
Uncertain significance(1); Benign(5); Likely benign(6)
15
criteria provided, conflicting classifications
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_007294.4(BRCA1):c.4186-10G>A
Variation ID: 55133 Accession: VCV000055133.48
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 17q21.31 17: 43082585 (GRCh38) [ NCBI UCSC ] 17: 41234602 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 4, 2014 Oct 8, 2024 Feb 1, 2024 - HGVS
- ... more HGVS ... less HGVS
- Protein change
- -
- Other names
-
IVS12-10G>A
- Canonical SPDI
- NC_000017.11:43082584:C:T
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
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.
-
0.00040 (T)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
The Genome Aggregation Database (gnomAD) 0.00000
Trans-Omics for Precision Medicine (TOPMed) 0.00003
Exome Aggregation Consortium (ExAC) 0.00027
The Genome Aggregation Database (gnomAD), exomes 0.00028
1000 Genomes Project 30x 0.00031
1000 Genomes Project 0.00040
- Links
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 | ||
|---|---|---|---|---|---|---|
| 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. |
|||
| BRCA1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
13044 | 14850 | |
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. |
|---|---|---|---|---|
| Likely benign (3) |
criteria provided, single submitter
|
Jul 24, 2017 | RCV000112287.10 | |
| Conflicting interpretations of pathogenicity (3) |
criteria provided, conflicting classifications
|
Aug 15, 2023 | RCV000212182.23 | |
| Benign/Likely benign (3) |
criteria provided, multiple submitters, no conflicts
|
Aug 3, 2020 | RCV000589275.17 | |
| Benign/Likely benign (2) |
criteria provided, multiple submitters, no conflicts
|
Apr 30, 2021 | RCV000771225.10 | |
| Benign/Likely benign (2) |
criteria provided, multiple submitters, no conflicts
|
Feb 1, 2024 | RCV001514091.14 | |
| Likely benign (1) |
criteria provided, single submitter
|
Nov 29, 2021 | RCV003149707.9 | |
|
BRCA1-related disorder
|
Likely benign (1) |
no assertion criteria provided
|
Apr 16, 2019 | RCV004554673.2 |
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. |
|
|---|---|---|---|---|---|
|
Uncertain significance
(Aug 19, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: no
Allele origin:
germline
|
Genetic Services Laboratory, University of Chicago
Accession: SCV000593679.1
First in ClinVar: Jul 24, 2016 Last updated: Jul 24, 2016 |
|
|
|
Likely benign
(Jul 24, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000785402.2
First in ClinVar: Apr 04, 2014 Last updated: Apr 04, 2014 |
|
|
|
Benign
(Apr 30, 2021)
|
criteria provided, single submitter
Method: curation
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Sema4, Sema4
Accession: SCV002538270.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022 |
|
|
|
Benign
(Oct 13, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
unknown
|
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000605869.4
First in ClinVar: Sep 30, 2017 Last updated: Dec 31, 2022 |
|
|
|
Likely benign
(Nov 29, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Breast and/or ovarian cancer
Affected status: unknown
Allele origin:
germline
|
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario
Accession: SCV003838727.1
First in ClinVar: Mar 11, 2023 Last updated: Mar 11, 2023 |
|
|
|
Benign
(Aug 15, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Accession: SCV002760927.3
First in ClinVar: Dec 17, 2022 Last updated: Aug 18, 2023 |
|
|
|
Benign
(Apr 22, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000699117.1
First in ClinVar: Mar 17, 2018 Last updated: Mar 17, 2018 |
Comment:
Variant summary: The c.4186-10G>A in BRCA1 gene is an intronic change that involves a non-conserved nucleotide. 4/5 programs in Alamut predict that this variant does … (more)
Variant summary: The c.4186-10G>A in BRCA1 gene is an intronic change that involves a non-conserved nucleotide. 4/5 programs in Alamut predict that this variant does not affect normal splicing, however no functional studies supporting this notion were published at the time of evaluation. The variant is present in the control population dataset of ExAC, mainly in individuals of East Asian descent at frequency of 0.17%, including one homozygous occurrence. The observed frequency exceeds the maximum expected allele frequency for a pathogenic BRCA1 variant, suggesting that it is a polymorphism. The fact that c.4186-10G>A has been reported to co-occur with two different deleterious mutation in BRCA1 gene (c.3700_3704delGTAAA and c.3759_3760delTA) suggests a non-disease causing nature of this variant. In addition, the variant has been reported as Polymorphismin published reports (Soumittra, 2009). Taken together, this variant has been classified as Benign. (less)
|
|
|
Likely benign
(Aug 21, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000903320.1
First in ClinVar: May 20, 2019 Last updated: May 20, 2019 |
|
|
|
Likely benign
(Aug 03, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV001472093.1
First in ClinVar: Jan 26, 2021 Last updated: Jan 26, 2021 |
|
|
|
Likely benign
(Jul 02, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000210170.11
First in ClinVar: Feb 24, 2015 Last updated: Apr 09, 2018 |
Comment:
In-silico analysis, which includes splice predictors and evolutionary conservation, is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, … (more)
In-silico analysis, which includes splice predictors and evolutionary conservation, is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; This variant is associated with the following publications: (PMID: 18627636, 16267036, 25561518, 26269718, 28222693, 29280214) (less)
|
|
|
Likely benign
(Nov 16, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: yes
Allele origin:
germline
|
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State
Accession: SCV002025942.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
Number of individuals with the variant: 2
Geographic origin: South Africa
Testing laboratory: National Health Laboratory Service (NHLS)
|
|
|
Benign
(Feb 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001721844.4
First in ClinVar: Jun 15, 2021 Last updated: Feb 28, 2024 |
|
|
|
Uncertain significance
(May 29, 2002)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial 1
Affected status: yes
Allele origin:
germline
|
Breast Cancer Information Core (BIC) (BRCA1)
Accession: SCV000145019.1
First in ClinVar: Apr 04, 2014 Last updated: Apr 04, 2014 |
Observation 1:
Number of individuals with the variant: 1
Observation 2:
Number of individuals with the variant: 1
Ethnicity/Population group: Indian
Geographic origin: Malaysia
Observation 3:
Number of individuals with the variant: 1
Ethnicity/Population group: Western European, Latin American, Caribbean
|
|
|
Benign
(Sep 13, 2010)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial 1
Affected status: not provided
Allele origin:
germline
|
Sharing Clinical Reports Project (SCRP)
Accession: SCV000297608.1
First in ClinVar: Apr 04, 2014 Last updated: Apr 04, 2014 |
|
|
|
Likely benign
(Apr 16, 2019)
|
no assertion criteria provided
Method: clinical testing
|
BRCA1-related condition
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV004755541.2
First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024 |
Comment:
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
|
|
| click to load more click to collapse | |||||
Comment:
Comment:
In-silico analysis, which includes splice predictors and evolutionary conservation, is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; This variant is associated with the following publications: (PMID: 18627636, 16267036, 25561518, 26269718, 28222693, 29280214)
Comment:
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Germline Functional Evidence
| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Comment:
Variant summary: The c.4186-10G>A in BRCA1 gene is an intronic change that involves a non-conserved nucleotide. 4/5 programs in Alamut predict that this variant does not affect normal splicing, however no functional studies supporting this notion were published at the time of evaluation. The variant is present in the control population dataset of ExAC, mainly in individuals of East Asian descent at frequency of 0.17%, including one homozygous occurrence. The observed frequency exceeds the maximum expected allele frequency for a pathogenic BRCA1 variant, suggesting that it is a polymorphism. The fact that c.4186-10G>A has been reported to co-occur with two different deleterious mutation in BRCA1 gene (c.3700_3704delGTAAA and c.3759_3760delTA) suggests a non-disease causing nature of this variant. In addition, the variant has been reported as Polymorphismin published reports (Soumittra, 2009). Taken together, this variant has been classified as Benign.
Comment:
In-silico analysis, which includes splice predictors and evolutionary conservation, is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; This variant is associated with the following publications: (PMID: 18627636, 16267036, 25561518, 26269718, 28222693, 29280214)
Comment:
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Prevalence of Clinically Relevant Germline BRCA Variants in a Large Unselected South African Breast and Ovarian Cancer Cohort: A Public Sector Experience. | Van der Merwe NC | Frontiers in genetics | 2022 | DOI: 10.3389/fgene.2022.834265 |
| Thorough in silico and in vitro cDNA analysis of 21 putative BRCA1 and BRCA2 splice variants and a complex tandem duplication in BRCA2 allowing the identification of activated cryptic splice donor sites in BRCA2 exon 11. | Baert A | Human mutation | 2018 | PMID: 29280214 |
| Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. | Richards S | Genetics in medicine : official journal of the American College of Medical Genetics | 2015 | PMID: 25741868 |
| Molecular genetics analysis of hereditary breast and ovarian cancer patients in India. | Soumittra N | Hereditary cancer in clinical practice | 2009 | PMID: 19656415 |
| Evaluation of BRCA1 and BRCA2 mutations and risk-prediction models in a typical Asian country (Malaysia) with a relatively low incidence of breast cancer. | Thirthagiri E | Breast cancer research : BCR | 2008 | PMID: 18627636 |
Text-mined citations for rs80358172 ...
HelpThese 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 Nov 10, 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.