ClinVar Genomic variation as it relates to human health
NM_017780.4(CHD7):c.1480C>T (p.Arg494Ter)
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.1480C>T (p.Arg494Ter)
Variation ID: 158279 Accession: VCV000158279.35
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 8q12.2 8: 60742912 (GRCh38) [ NCBI UCSC ] 8: 61655471 (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 Feb 14, 2024 Jan 14, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_017780.4:c.1480C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_060250.2:p.Arg494Ter nonsense NM_001316690.1:c.1480C>T NP_001303619.1:p.Arg494Ter nonsense NM_017780.3:c.[1480C>T] NC_000008.11:g.60742912C>T NC_000008.10:g.61655471C>T NG_007009.1:g.69133C>T LRG_176:g.69133C>T LRG_176t1:c.1480C>T - Protein change
- R494*
- Other names
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- Canonical SPDI
- NC_000008.11:60742911: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.
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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 |
3241 | 3441 |
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 (7) |
criteria provided, multiple submitters, no conflicts
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Jan 14, 2024 | RCV000145653.21 | |
Pathogenic (6) |
criteria provided, multiple submitters, no conflicts
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Nov 22, 2022 | RCV000413726.19 |
Submissions - Germline
Classification
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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 08, 2013)
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criteria provided, single submitter
Method: clinical testing
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CHARGE syndrome
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
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Genetic Services Laboratory, University of Chicago
Accession: SCV000192753.1
First in ClinVar: Nov 23, 2014 Last updated: Nov 23, 2014 |
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Pathogenic
(Aug 01, 2017)
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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: SCV000603085.2
First in ClinVar: Sep 30, 2017 Last updated: Feb 17, 2019 |
Comment:
The CHD7 c.1480C>T; p.Arg494Ter variant (rs587783429) induces an early termination codon and is predicted to result in a truncated protein or absent transcript. This variant … (more)
The CHD7 c.1480C>T; p.Arg494Ter variant (rs587783429) induces an early termination codon and is predicted to result in a truncated protein or absent transcript. This variant has previously been reported in individuals with CHARGE syndrome (Lalani 2006, see ClinVar link), and is absent from general population databases (Exome Variant Server, Genome Aggregation Database). Therefore, this variant is considered pathogenic. REFERENCES Link to ClinVar database for p.Arg494Ter: https://www.ncbi.nlm.nih.gov/clinvar/variation/158279/ Lalani SR et al. Spectrum of CHD7 mutations in 110 individuals with CHARGE syndrome and genotype-phenotype correlation. Am J Hum Genet. 2006 Feb;78(2):303-14. (less)
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Pathogenic
(Nov 30, 2018)
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criteria provided, single submitter
Method: clinical testing
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CHARGE association
Affected status: yes
Allele origin:
unknown
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Centre for Mendelian Genomics, University Medical Centre Ljubljana
Accession: SCV001368583.2
First in ClinVar: Jul 04, 2020 Last updated: Dec 12, 2020 |
Comment:
This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PM2,PP4,PP5.
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Pathogenic
(Feb 01, 2021)
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criteria provided, single submitter
Method: clinical testing
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not provided
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
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Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001480182.1
First in ClinVar: Feb 20, 2021 Last updated: Feb 20, 2021 |
Clinical Features:
Global developmental delay (present) , Immunodeficiency (present)
Sex: female
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Pathogenic
(Apr 02, 2020)
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criteria provided, single submitter
Method: clinical testing
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CHARGE association
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
unknown
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Genomic Medicine Lab, University of California San Francisco
Study: CSER-P3EGS
Accession: SCV001573074.1 First in ClinVar: May 10, 2021 Last updated: May 10, 2021 |
Sex: male
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Pathogenic
(-)
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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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Neuberg Centre For Genomic Medicine, NCGM
Accession: SCV002072910.1
First in ClinVar: Feb 03, 2022 Last updated: Feb 03, 2022 |
Comment:
The stop gained p.R494* in CHD7 (NM_017780.4) has been reported previously reported in affected patients (Janssen N et al; Lalani SR et al). The variant … (more)
The stop gained p.R494* in CHD7 (NM_017780.4) has been reported previously reported in affected patients (Janssen N et al; Lalani SR et al). The variant has been submitted to ClinVar as Pathogenic. The p.R494* variant is novel (not in any individuals) in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function mutations have been previously described to be disease causing. For these reasons, this variant has been classified as Pathogenic. (less)
Clinical Features:
Failure to thrive (present)
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Pathogenic
(Aug 22, 2022)
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criteria provided, single submitter
Method: clinical testing
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CHARGE association
Affected status: yes
Allele origin:
unknown
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Daryl Scott Lab, Baylor College of Medicine
Accession: SCV002567934.1
First in ClinVar: Aug 29, 2022 Last updated: Aug 29, 2022 |
Number of individuals with the variant: 1
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Pathogenic
(Nov 22, 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: SCV000490461.4
First in ClinVar: Jan 09, 2017 Last updated: Dec 03, 2022 |
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 in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 16400610, 30181649, 25525159, 29453417, 22461308, 24368733, 21158681, 23024289, 28832562, 32625235, 34009138, 31785789) (less)
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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: SCV000328321.2
First in ClinVar: Nov 23, 2014 Last updated: Mar 04, 2023
Comment:
Clinical Testing
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Number of individuals with the variant: 1
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Pathogenic
(Nov 10, 2021)
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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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Revvity Omics, Revvity
Accession: SCV002019272.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Pathogenic
(Jan 14, 2024)
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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: SCV001224818.5
First in ClinVar: Apr 15, 2020 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Arg494*) in the CHD7 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Arg494*) 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). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with clinical features of CHARGE syndrome (PMID: 16400610, 21158681, 22461308, 23024289, 24368733, 28832562). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 158279). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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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: SCV002036789.1 First in ClinVar: Dec 18, 2021 Last updated: Dec 18, 2021 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
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: SCV002037454.1 First in ClinVar: Dec 21, 2021 Last updated: Dec 21, 2021 |
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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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A clinically driven variant prioritization framework outperforms purely computational approaches for the diagnostic analysis of singleton WES data. | Stark Z | European journal of human genetics : EJHG | 2017 | PMID: 28832562 |
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 |
Deregulated FGF and homeotic gene expression underlies cerebellar vermis hypoplasia in CHARGE syndrome. | Yu T | eLife | 2013 | PMID: 24368733 |
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 |
Mutations in the CHD7 gene: the experience of a commercial laboratory. | Bartels CF | Genetic testing and molecular biomarkers | 2010 | PMID: 21158681 |
Spectrum of CHD7 mutations in 110 individuals with CHARGE syndrome and genotype-phenotype correlation. | Lalani SR | American journal of human genetics | 2006 | PMID: 16400610 |
Text-mined citations for rs587783429 ...
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.