ClinVar Genomic variation as it relates to human health
NM_004004.6(GJB2):c.*1C>T
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.
Uncertain significance(2); Benign(2); Likely benign(7)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_004004.6(GJB2):c.*1C>T
Variation ID: 44715 Accession: VCV000044715.27
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 13q12.11 13: 20188900 (GRCh38) [ NCBI UCSC ] 13: 20763039 (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 Nov 23, 2014 Oct 8, 2024 Aug 31, 2020 - HGVS
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Nucleotide Protein Molecular
consequenceNM_004004.6:c.*1C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
3 prime UTR NC_000013.11:g.20188900G>A NC_000013.10:g.20763039G>A NG_008358.1:g.9076C>T LRG_1350:g.9076C>T LRG_1350t1:c.*1C>T - Protein change
- Other names
- c.*1C>T
- Canonical SPDI
- NC_000013.11:20188899:G:A
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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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0.00080 (A)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00039
Exome Aggregation Consortium (ExAC) 0.00042
The Genome Aggregation Database (gnomAD) 0.00045
The Genome Aggregation Database (gnomAD), exomes 0.00054
Trans-Omics for Precision Medicine (TOPMed) 0.00076
1000 Genomes Project 0.00080
1000 Genomes Project 30x 0.00109
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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GJB2 | Dosage sensitivity unlikely | No evidence available |
GRCh38 GRCh37 |
569 | 636 |
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/Likely benign (2) |
criteria provided, multiple submitters, no conflicts
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Feb 8, 2013 | RCV000037802.23 | |
Likely benign (1) |
criteria provided, single submitter
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Apr 27, 2017 | RCV000344717.13 | |
Likely benign (1) |
criteria provided, single submitter
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Apr 27, 2017 | RCV000296648.13 | |
Conflicting interpretations of pathogenicity (4) |
criteria provided, conflicting classifications
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Aug 21, 2019 | RCV000586188.22 | |
Conflicting interpretations of pathogenicity (3) |
criteria provided, conflicting classifications
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May 24, 2018 | RCV000674792.16 | |
Likely benign (1) |
criteria provided, single submitter
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Aug 31, 2020 | RCV001257161.9 | |
GJB2-related disorder
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Likely benign (1) |
no assertion criteria provided
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Aug 6, 2024 | RCV004734551.1 |
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
(Feb 08, 2013)
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criteria provided, single submitter
Method: clinical testing
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not specified
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
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Genetic Services Laboratory, University of Chicago
Accession: SCV000193152.1
First in ClinVar: Nov 23, 2014 Last updated: Nov 23, 2014 |
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Uncertain significance
(Oct 27, 2014)
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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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Eurofins Ntd Llc (ga)
Accession: SCV000112256.8
First in ClinVar: Jan 17, 2014 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 2
Sex: mixed
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Likely benign
(Apr 27, 2017)
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criteria provided, single submitter
Method: clinical testing
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Autosomal dominant nonsyndromic hearing loss 3A
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000382989.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
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Likely benign
(Apr 27, 2017)
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criteria provided, single submitter
Method: clinical testing
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Ichthyosis, hystrix-like, with hearing loss
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000382988.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
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Likely benign
(Apr 27, 2017)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive nonsyndromic hearing loss 1A
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000382987.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
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Likely benign
(Jul 22, 2019)
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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: SCV001818675.1
First in ClinVar: Sep 08, 2021 Last updated: Sep 08, 2021 |
Comment:
This variant is associated with the following publications: (PMID: 20022641, 17666888, 22567369, 15744158, 17041943)
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Benign
(May 31, 2016)
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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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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000698222.1
First in ClinVar: Mar 17, 2018 Last updated: Mar 17, 2018 |
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Uncertain significance
(May 24, 2018)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive nonsyndromic hearing loss 1A
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000800190.1
First in ClinVar: Aug 05, 2018 Last updated: Aug 05, 2018 |
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Likely benign
(Jun 03, 2011)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: not provided
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000061464.5
First in ClinVar: May 03, 2013 Last updated: Dec 06, 2016 |
Comment:
The *1C>T variant was identified in the 3?UTR of GJB2. This variant is located 1 base after the termination codon. Although, this variant has been … (more)
The *1C>T variant was identified in the 3?UTR of GJB2. This variant is located 1 base after the termination codon. Although, this variant has been detected in i ndividuals with hearing loss, it has never been identified with a second pathoge nic GJB2 variant (Frei 2005, Samanich 2007, Tang 2006, Rabionet unpublished). In addition, it was identified at an equal frequency (0.5%) in control chromosomes (Samanich 2007). In summary, the *1C>T variant is not expected to have clinical or pathological significance because it is not predicted to affect the transcri pt and has been found at an equal frequency in controls. (less)
Number of individuals with the variant: 1
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Likely benign
(Aug 31, 2020)
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criteria provided, single submitter
Method: clinical testing
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Nonsyndromic hearing loss and deafness
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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INGEBI, INGEBI / CONICET
Accession: SCV001433679.1
First in ClinVar: Sep 27, 2020 Last updated: Sep 27, 2020 |
Comment:
Based on ACMG/AMP guidelines and Hearing Loss Expert Panel specific criteria: the filtering allele frequency of the c.*1C>T variant in GJB2 gene is 0,16% in … (more)
Based on ACMG/AMP guidelines and Hearing Loss Expert Panel specific criteria: the filtering allele frequency of the c.*1C>T variant in GJB2 gene is 0,16% in latino population (72/35366 alleles with 95%CI) from Genome Aggregation Database (http://gnomad.broadinstitute.org; calculated by using inverse allele frequency at https://www.cardiodb.org/allelefrequencyapp/), which meets the BS1_Supporting rule. Bening computational veredict prediction from DANN and CADD predictors applying for BP4 rule. In summary, the c.*1C>T variant meets criteria to be classified likely benign (BS1_Supporting, BP4) (less)
Number of individuals with the variant: 2
Clinical Features:
Prelingual profound hearing loss (present)
Family history: yes
Sex: female
Ethnicity/Population group: Caucasian
Geographic origin: Argentina
Tissue: blood
Secondary finding: no
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Likely benign
(Aug 21, 2019)
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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: SCV001157394.2
First in ClinVar: Feb 10, 2020 Last updated: Jan 26, 2021 |
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Uncertain significance
(May 19, 2020)
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no assertion criteria provided
Method: clinical testing
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Autosomal recessive deafness type 1A
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV001463928.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
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Likely benign
(Aug 06, 2024)
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no assertion criteria provided
Method: clinical testing
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GJB2-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV005351506.1
First in ClinVar: Oct 08, 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).
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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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Non-syndromic hearing impairment in a multi-ethnic population of Northeastern Brazil. | Manzoli GN | International journal of pediatric otorhinolaryngology | 2013 | PMID: 23684175 |
Assessing Noncoding Sequence Variants of GJB2 for Hearing Loss Association. | Matos TD | Genetics research international | 2011 | PMID: 22567369 |
Prevalence of DFNB1 mutations in Argentinean children with non-syndromic deafness. Report of a novel mutation in GJB2. | Gravina LP | International journal of pediatric otorhinolaryngology | 2010 | PMID: 20022641 |
GJB2 and GJB6 genes: molecular study and identification of novel GJB2 mutations in the hearing-impaired Argentinean population. | Dalamón V | Audiology & neuro-otology | 2010 | PMID: 19887791 |
A multicenter study of the frequency and distribution of GJB2 and GJB6 mutations in a large North American cohort. | Putcha GV | Genetics in medicine : official journal of the American College of Medical Genetics | 2007 | PMID: 17666888 |
Mutations in GJB2, GJB6, and mitochondrial DNA are rare in African American and Caribbean Hispanic individuals with hearing impairment. | Samanich J | American journal of medical genetics. Part A | 2007 | PMID: 17357124 |
DNA sequence analysis of GJB2, encoding connexin 26: observations from a population of hearing impaired cases and variable carrier rates, complex genotypes, and ethnic stratification of alleles among controls. | Tang HY | American journal of medical genetics. Part A | 2006 | PMID: 17041943 |
GJB2 mutations in hearing impairment: identification of a broad clinical spectrum for improved genetic counseling. | Frei K | The Laryngoscope | 2005 | PMID: 15744158 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=GJB2 | - | - | - | - |
Text-mined citations for rs111033327 ...
HelpRecord last updated Oct 13, 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.