ClinVar Genomic variation as it relates to human health
NM_017780.4(CHD7):c.469C>T (p.Arg157Ter)
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_017780.4(CHD7):c.469C>T (p.Arg157Ter)
Variation ID: 195321 Accession: VCV000195321.25
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 8q12.2 8: 60741901 (GRCh38) [ NCBI UCSC ] 8: 61654460 (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 Jun 28, 2015 May 1, 2024 May 29, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_017780.4:c.469C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_060250.2:p.Arg157Ter nonsense NM_001316690.1:c.469C>T NP_001303619.1:p.Arg157Ter nonsense NC_000008.11:g.60741901C>T NC_000008.10:g.61654460C>T NG_007009.1:g.68122C>T LRG_176:g.68122C>T LRG_176t1:c.469C>T - Protein change
- R157*
- Other names
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- Canonical SPDI
- NC_000008.11:60741900:C:T
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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.
The Genome Aggregation Database (gnomAD), exomes 0.00000
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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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
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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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CHD7 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
3244 | 3444 |
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 (5) |
criteria provided, multiple submitters, no conflicts
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May 29, 2023 | RCV000175883.16 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Feb 17, 2022 | RCV000351604.8 | |
Pathogenic (1) |
criteria provided, single submitter
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Feb 17, 2017 | RCV000506348.8 | |
Pathogenic (1) |
criteria provided, single submitter
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Nov 4, 2016 | RCV002336428.2 |
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
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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
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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
(Feb 17, 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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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000603080.1
First in ClinVar: Sep 30, 2017 Last updated: Sep 30, 2017 |
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Pathogenic
(Sep 10, 2018)
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criteria provided, single submitter
Method: clinical testing
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CHARGE association
Affected status: yes
Allele origin:
de novo
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Baylor Genetics
Accession: SCV001527961.1
First in ClinVar: Mar 22, 2021 Last updated: Mar 22, 2021 |
Comment:
This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
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Pathogenic
(May 13, 2021)
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criteria provided, single submitter
Method: clinical testing
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CHARGE association
Affected status: yes
Allele origin:
germline
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Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein
Accession: SCV002512590.1
First in ClinVar: May 21, 2022 Last updated: May 21, 2022 |
Comment:
ACMG classification criteria: PVS1 very strong, PS4 moderate, PM2 moderate, PM6 strong, PP1
Geographic origin: Brazil
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Pathogenic
(May 29, 2023)
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criteria provided, single submitter
Method: clinical testing
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CHARGE association
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000946741.6
First in ClinVar: Aug 14, 2019 Last updated: Feb 14, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 195321). This premature translational stop signal … (more)
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 195321). This premature translational stop signal has been observed in individual(s) with CHARGE syndrome (PMID: 15300250, 16155193, 17661815, 20624498, 21158681, 22461308, 23024289, 26538304; Invitae). In at least one individual the variant was observed to be de novo. It has also been observed to segregate with disease in related individuals. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change creates a premature translational stop signal (p.Arg157*) in the CHD7 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CHD7 are known to be pathogenic (PMID: 22461308, 25077900). (less)
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Pathogenic
(Jul 22, 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: SCV000227454.5
First in ClinVar: Jun 28, 2015 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 1
Sex: mixed
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Pathogenic
(Oct 18, 2021)
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criteria provided, single submitter
Method: clinical testing
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CHARGE association
Affected status: yes
Allele origin:
de novo
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Equipe Genetique des Anomalies du Developpement, Université de Bourgogne
Accession: SCV001985058.1
First in ClinVar: Oct 30, 2021 Last updated: Oct 30, 2021 |
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Pathogenic
(Sep 05, 2016)
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criteria provided, single submitter
Method: clinical testing
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CHARGE syndrome
Affected status: yes
Allele origin:
germline
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Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia
Accession: SCV000328314.2
First in ClinVar: Jun 28, 2015 Last updated: Mar 04, 2023
Comment:
Clinical Testing
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Number of individuals with the variant: 1
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Pathogenic
(Feb 17, 2022)
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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: SCV000329256.8
First in ClinVar: Dec 06, 2016 Last updated: Mar 04, 2023 |
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not … (more)
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 21554267, 21856375, 16155193, 21158681, 22461308, 17661815, 20624498, 21378379, 15300250, 26538304, 23024289) (less)
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Pathogenic
(Nov 04, 2016)
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criteria provided, single submitter
Method: clinical testing
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Inborn genetic diseases
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV002637837.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The p.R157* variant (also known as c.469C>T), located in coding exon 1 of the CHD7 gene, results from a C to T substitution at nucleotide … (more)
The p.R157* variant (also known as c.469C>T), located in coding exon 1 of the CHD7 gene, results from a C to T substitution at nucleotide position 469. This changes the amino acid from an arginine to a stop codon within coding exon 1. This mutation has been detected in several individuals with CHARGE syndrome diagnoses and in others who only presented with minor diagnostic criteria features (Sohn YB et al. J. Hum. Genet., 2016 Mar;61:235-9). (Vissers LE et al. Nat. Genet., 2004 Sep;36:955-7). (Delahaye A et al. Clin. Genet., 2007 Aug;72:112-21). In addition to the clinical data presented in the literature, 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)
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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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Cerebellar vermis hypoplasia in CHARGE syndrome: clinical and molecular characterization of 18 unrelated Korean patients. | Sohn YB | Journal of human genetics | 2016 | PMID: 26538304 |
The prevalence of CHD7 missense versus truncating mutations is higher in patients with Kallmann syndrome than in typical CHARGE patients. | Marcos S | The Journal of clinical endocrinology and metabolism | 2014 | PMID: 25077900 |
Antenatal spectrum of CHARGE syndrome in 40 fetuses with CHD7 mutations. | Legendre M | Journal of medical genetics | 2012 | PMID: 23024289 |
Mutation update on the CHD7 gene involved in CHARGE syndrome. | Janssen N | Human mutation | 2012 | PMID: 22461308 |
CHD7 mutations causing CHARGE syndrome are predominantly of paternal origin. | Pauli S | Clinical genetics | 2012 | PMID: 21554267 |
Mutations in the CHD7 gene: the experience of a commercial laboratory. | Bartels CF | Genetic testing and molecular biomarkers | 2010 | PMID: 21158681 |
Novel CHD7 mutations contributing to the mutation spectrum in patients with CHARGE syndrome. | Wessels K | European journal of medical genetics | 2010 | PMID: 20624498 |
Familial CHARGE syndrome because of CHD7 mutation: clinical intra- and interfamilial variability. | Delahaye A | Clinical genetics | 2007 | PMID: 17661815 |
CHARGE syndrome: the phenotypic spectrum of mutations in the CHD7 gene. | Jongmans MC | Journal of medical genetics | 2006 | PMID: 16155193 |
Mutations in a new member of the chromodomain gene family cause CHARGE syndrome. | Vissers LE | Nature genetics | 2004 | PMID: 15300250 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=CHD7 | - | - | - | - |
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Text-mined citations for rs794727293 ...
HelpRecord last updated May 08, 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.