This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
ClinVar Genomic variation as it relates to human health
NM_000053.4(ATP7B):c.1216T>G (p.Ser406Ala)
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.
(21)
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.
Benign/Likely benign
21
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000053.4(ATP7B):c.1216T>G (p.Ser406Ala)
Variation ID: 35701 Accession: VCV000035701.43
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 13q14.3 13: 51974004 (GRCh38) [ NCBI UCSC ] 13: 52548140 (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, 2013 Sep 29, 2024 Feb 5, 2024 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000053.4:c.1216T>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000044.2:p.Ser406Ala missense NM_001005918.3:c.1216T>G NP_001005918.1:p.Ser406Ala missense NM_001243182.2:c.883T>G NP_001230111.1:p.Ser295Ala missense NM_001330578.2:c.1216T>G NP_001317507.1:p.Ser406Ala missense NM_001330579.2:c.1216T>G NP_001317508.1:p.Ser406Ala missense NC_000013.11:g.51974004A>C NC_000013.10:g.52548140A>C NG_008806.1:g.42491T>G P35670:p.Ser406Ala - Protein change
- S406A, S295A
- Other names
- -
- Canonical SPDI
- NC_000013.11:51974003:A:C
-
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.
-
0.37620 (C)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
1000 Genomes Project 30x 0.37399
1000 Genomes Project 0.37620
Trans-Omics for Precision Medicine (TOPMed) 0.38546
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.40122
The Genome Aggregation Database (gnomAD) 0.41549
- 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. |
|||
| ATP7B | - | - |
GRCh38 GRCh37 |
2915 | 3059 | |
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. |
|---|---|---|---|---|
| Benign/Likely benign (9) |
criteria provided, multiple submitters, no conflicts
|
Feb 5, 2024 | RCV000029350.40 | |
| Benign (9) |
criteria provided, multiple submitters, no conflicts
|
Apr 27, 2016 | RCV000078038.32 | |
| Benign (2) |
criteria provided, single submitter
|
- | RCV001354129.10 | |
| Benign (1) |
criteria provided, single submitter
|
Jul 1, 2016 | RCV002354169.9 |
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. |
|
|---|---|---|---|---|---|
|
Benign
(-)
|
criteria provided, single submitter
Method: clinical testing
|
NOT SPECIFIED
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV000301692.1
First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016 |
|
|
|
Benign
(Jan 13, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Wilson disease
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000384680.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
|
|
|
benign
(Aug 18, 2011)
|
criteria provided, single submitter
Method: clinical testing
|
Wilson Disease
(autosomal unknown)
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000051996.2
First in ClinVar: Apr 04, 2013 Last updated: Apr 11, 2022 |
Comment:
Converted during submission to Benign.
Observation 1:
Tissue: Blood
Observation 2:
Tissue: Blood
Observation 3:
Tissue: Blood
Observation 4:
Tissue: Blood
Observation 5:
Tissue: Blood
Observation 6:
Tissue: Blood
Observation 7:
Tissue: Blood
Observation 8:
Tissue: Blood
Observation 9:
Tissue: Blood
Observation 10:
Tissue: Blood
Observation 11:
Tissue: Blood
Observation 12:
Tissue: Blood
Observation 13:
Tissue: Blood
Observation 14:
Tissue: Blood
Observation 15:
Tissue: Blood
Observation 16:
Tissue: Blood
Observation 17:
Tissue: Blood
Observation 18:
Tissue: Blood
Observation 19:
Tissue: Blood
Observation 20:
Tissue: Blood
Observation 21:
Tissue: Blood
Observation 22:
Tissue: Blood
Observation 23:
Tissue: Blood
Observation 24:
Tissue: Blood
Observation 25:
Tissue: Blood
Observation 26:
Tissue: Blood
Observation 27:
Tissue: Blood
Observation 28:
Tissue: Blood
Observation 29:
Tissue: Blood
Observation 30:
Tissue: Blood
Observation 31:
Tissue: Blood
Observation 32:
Tissue: Blood
Observation 33:
Tissue: Blood
Observation 34:
Tissue: Blood
Observation 35:
Tissue: Blood
Observation 36:
Tissue: Blood
Observation 37:
Tissue: Blood
Observation 38:
Tissue: Blood
Observation 39:
Tissue: Blood
Observation 40:
Tissue: Blood
Observation 41:
Tissue: Blood
Observation 42:
Tissue: Blood
Observation 43:
Tissue: Blood
Observation 44:
Tissue: Blood
Observation 45:
Tissue: Blood
Observation 46:
Tissue: Blood
Observation 47:
Tissue: Blood
Observation 48:
Tissue: Blood
Observation 49:
Tissue: Blood
Observation 50:
Tissue: Blood
Observation 51:
Tissue: Blood
Observation 52:
Tissue: Blood
Observation 53:
Tissue: Blood
Observation 54:
Tissue: Blood
|
|
|
Benign
(Feb 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Wilson disease
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001728177.4
First in ClinVar: Jun 15, 2021 Last updated: Feb 20, 2024 |
|
|
|
Likely benign
(Nov 29, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Wilson disease
Affected status: unknown
Allele origin:
germline
|
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000602590.10
First in ClinVar: Mar 08, 2017 Last updated: Feb 20, 2024 |
|
|
|
Benign
(Feb 05, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Wilson disease
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
|
All of Us Research Program, National Institutes of Health
Accession: SCV004846341.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024
Comment:
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of … (more)
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of variant classification. Additional details can be found in publication PMID: 35346344, PMCID: PMC8962531 (less)
|
Number of individuals with the variant: 74716
|
|
|
Benign
(-)
|
criteria provided, single submitter
Method: not provided
|
not provided
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
|
Breakthrough Genomics, Breakthrough Genomics
Accession: SCV005230383.1
First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024 |
|
|
|
Benign
(Feb 08, 2013)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
|
Genetic Services Laboratory, University of Chicago
Accession: SCV000192308.1
First in ClinVar: Nov 23, 2014 Last updated: Nov 23, 2014 |
|
|
|
Benign
(Jan 08, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000517533.4
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more)
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
|
|
|
Benign
(Apr 27, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000109876.8
First in ClinVar: Jan 17, 2014 Last updated: Mar 08, 2017 |
Number of individuals with the variant: 43
Sex: mixed
|
|
|
Benign
(Jul 01, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Wilson disease
Affected status: no
Allele origin:
germline
|
Genome-Nilou Lab
Accession: SCV001750141.1
First in ClinVar: Jul 18, 2021 Last updated: Jul 18, 2021 |
Sex: mixed
|
|
|
Benign
(Mar 05, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Wilson disease
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV004362502.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
|
|
|
Benign
(Jul 01, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Inborn genetic diseases
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV002654451.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation … (more)
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
|
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Genome Diagnostics Laboratory, Amsterdam University Medical Center
Study: VKGL Data-share Consensus
Accession: SCV001807033.1 First in ClinVar: Aug 27, 2021 Last updated: Aug 27, 2021 |
|
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Clinical Genetics, Academic Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001925486.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021 |
|
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001927634.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021 |
|
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
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: SCV001953377.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
|
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001975342.1 First in ClinVar: Oct 08, 2021 Last updated: Oct 08, 2021 |
|
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
Wilson disease
Affected status: yes
Allele origin:
germline
|
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV000733364.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
|
|
|
Benign
(Sep 16, 2020)
|
no assertion criteria provided
Method: clinical testing
|
Wilson disease
Affected status: unknown
Allele origin:
germline
|
Natera, Inc.
Accession: SCV001463852.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
|
|
|
Uncertain significance
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
unknown
|
Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV001548670.1 First in ClinVar: Apr 13, 2021 Last updated: Apr 13, 2021 |
Comment:
multiple AR variants in same gene - keep for nowAllele frequency is common in at least one population database (frequency: 54.463% in ExAC) based on … (more)
multiple AR variants in same gene - keep for nowAllele frequency is common in at least one population database (frequency: 54.463% in ExAC) based on the frequency threshold of 2.434% for this gene.Variant was observed in a homozygous state in population databases more than expected for disease. (less)
|
|
| click to load more click to collapse | |||||
Comment:
Comment:
Converted during submission to Benign.
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Comment:
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Comment:
multiple AR variants in same gene - keep for nowAllele frequency is common in at least one population database (frequency: 54.463% in ExAC) based on the frequency threshold of 2.434% for this gene.Variant was observed in a homozygous state in population databases more than expected for disease.
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:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Comment:
Converted during submission to Benign.
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Comment:
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Comment:
multiple AR variants in same gene - keep for nowAllele frequency is common in at least one population database (frequency: 54.463% in ExAC) based on the frequency threshold of 2.434% for this gene.Variant was observed in a homozygous state in population databases more than expected for disease.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Mutation analysis and the correlation between genotype and phenotype of Arg778Leu mutation in chinese patients with Wilson disease. | Wu ZY | Archives of neurology | 2001 | PMID: 11405812 |
| Determination of the frequencies of ten allelic variants of the Wilson disease gene (ATP7B), in pooled DNA samples. | Olsson C | European journal of human genetics : EJHG | 2000 | PMID: 11175281 |
| Identification and analysis of mutations in the Wilson disease gene (ATP7B): population frequencies, genotype-phenotype correlation, and functional analyses. | Shah AB | American journal of human genetics | 1997 | PMID: 9311736 |
| The Wilson disease gene: spectrum of mutations and their consequences. | Thomas GR | Nature genetics | 1995 | PMID: 7626145 |
| http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=ATP7B | - | - | - | - |
Text-mined citations for rs1801243 ...
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 03, 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.