ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.1389_1390delinsG (p.Thr464fs)
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.1389_1390delinsG (p.Thr464fs)
Variation ID: 37409 Accession: VCV000037409.11
- Type and length
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Indel, 2 bp
- Location
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Cytogenetic: 17q21.31 17: 43094141-43094142 (GRCh38) [ NCBI UCSC ] 17: 41246158-41246159 (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 Nov 29, 2022 Sep 8, 2016 - HGVS
- ... more HGVS ... less HGVS
- Protein change
- T417fs, T464fs, T352fs, T376fs, T422fs, T461fs, T168fs, T337fs, T353fs, T375fs, T437fs, T438fs, T296fs, T336fs, T397fs, T416fs, T423fs, T463fs, T393fs, T394fs, T396fs
- Other names
- 1508delAAinsG
- Canonical SPDI
- NC_000017.11:43094140:TT:C
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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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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Allele frequency
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The frequency of the allele represented by this VCV record.
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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
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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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
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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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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Pathogenic (3) |
reviewed by expert panel
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Sep 8, 2016 | RCV000030990.7 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 9, 2019 | RCV000213424.4 | |
Pathogenic (1) |
criteria provided, single submitter
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Mar 20, 2015 | RCV000487351.2 | |
Pathogenic (1) |
criteria provided, single submitter
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Apr 2, 2018 | RCV000462415.7 |
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
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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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Pathogenic
(Sep 08, 2016)
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reviewed by expert panel
Method: curation
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Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
germline
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Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)
Accession: SCV000299592.2
First in ClinVar: Sep 24, 2016 Last updated: Sep 24, 2016 |
Comment:
Variant allele predicted to encode a truncated non-functional protein.
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Pathogenic
(Apr 02, 2018)
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criteria provided, single submitter
Method: clinical testing
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Hereditary breast and ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000918677.1
First in ClinVar: Jun 02, 2019 Last updated: Jun 02, 2019 |
Comment:
Variant summary: BRCA1 c.1389_1390delinsG (p.Thr464ProfsX11) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more)
Variant summary: BRCA1 c.1389_1390delinsG (p.Thr464ProfsX11) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (eg. c.1480C>T (p.Gln494X), c.1492delC (p.Leu498fsX5), and c.1508delA (p.Lys503fsX29)). The variant was absent in 245916 control chromosomes (gnomAD). The variant, c.1389_1390delinsG, has not been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer. However, other variants such as c.1390delA (legacy names: c.1387delA, 1506delA) and c.1386delA (legacy name: 1505delG) that cause the same frameshift mutation have been reported in affected HBOC patients (Couch_1996, Peyrat_1998, Rebbeck_2016). Multiple ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as "pathogenic." Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Mar 20, 2015)
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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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GeneDx
Accession: SCV000566059.3
First in ClinVar: Apr 27, 2017 Last updated: Apr 27, 2017 |
Comment:
This combined deletion and insertion is denoted c.1389_1390delAAinsG at the cDNA level and p.Thr464ProfsX11 (T464PfsX11) at the protein level. Using alternate nomenclature, this variant would … (more)
This combined deletion and insertion is denoted c.1389_1390delAAinsG at the cDNA level and p.Thr464ProfsX11 (T464PfsX11) at the protein level. Using alternate nomenclature, this variant would be defined as c.1508delAAinsG. The normal sequence, with the bases that are deleted and inserted in brackets, is GGAA[delAA][insG]CCTA. The variant causes a frameshift, which changes a Threonine to a Proline at codon 464, and creates a premature stop codon at position 11 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. We consider BRCA1 c.1389_1390delAAinsG to be pathogenic. (less)
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Pathogenic
(Jan 09, 2019)
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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: SCV000278779.6
First in ClinVar: May 29, 2016 Last updated: Nov 29, 2022 |
Comment:
The c.1389_1390delAAinsG pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from the deletion of two nucleotides and insertion of one nucleotide … (more)
The c.1389_1390delAAinsG pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from the deletion of two nucleotides and insertion of one nucleotide causing a translational frameshift with a predicted alternate stop codon (p.T464Pfs*11). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. (less)
Number of individuals with the variant: 1
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Pathogenic
(Oct 29, 2001)
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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: SCV000144078.1
First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
Number of individuals with the variant: 1
Ethnicity/Population group: Mexican
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Pathogenic
(Dec 23, 2010)
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no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial 1
Affected status: not provided
Allele origin:
germline
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Sharing Clinical Reports Project (SCRP)
Accession: SCV000053582.3
First in ClinVar: Apr 04, 2013 Last updated: Sep 27, 2014 |
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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. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Inheritance of deleterious mutations at both BRCA1 and BRCA2 in an international sample of 32,295 women. | Rebbeck TR | Breast cancer research : BCR | 2016 | PMID: 27836010 |
Germline BRCA1 mutations in patients from 84 families with breast and/or ovarian cancers in northern France. | Peyrat JP | European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP) | 1998 | PMID: 10866029 |
Mutations and polymorphisms in the familial early-onset breast cancer (BRCA1) gene. Breast Cancer Information Core. | Couch FJ | Human mutation | 1996 | PMID: 8807330 |
Text-mined citations for rs273897659 ...
HelpRecord last updated Mar 30, 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.