Variant summary: The c.3015C>T (p.Asn1005=) in ATP7B gene is a synonymous change that involves a non-conserved nucleotide. 5/5 programs in Alamut predict that this variant does not affect normal splicing, however no functional studies supporting this notion were published at the time of evaluation. The variant is present in the control population dataset of ExAC at frequency of 0.0020 (123/60690 chrs tested), predominantly in individuals of African origin (0.02; 110/5328 chrs, including 2 homozygous occurrences). The observed frequency exceeds the maximum expected allele frequency for a pathogenic variant in this gene (0.0054), suggesting that it is a benign polymorphism. The variant was identified in at least 1 HBOC pt without strong evidence for causality. The variant of interest has not, to our knowledge, been identified in affected individuals via published reports, but is cited as Benign/Likely Benign by reputable database/clinical laboratories. Taken together, based on the prevalence in general population the variant was classified as Benign.
ClinVar Genomic variation as it relates to human health
NM_000053.4(ATP7B):c.3015C>T (p.Asn1005=)
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.
(12)
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
12
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.3015C>T (p.Asn1005=)
Variation ID: 35715 Accession: VCV000035715.35
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 13q14.3 13: 51946329 (GRCh38) [ NCBI UCSC ] 13: 52520465 (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 Oct 2, 2016 Oct 20, 2024 Feb 5, 2024 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000053.4:c.3015C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000044.2:p.Asn1005= synonymous NM_001005918.3:c.2394C>T NP_001005918.1:p.Asn798= synonymous NM_001243182.2:c.2682C>T NP_001230111.1:p.Asn894= synonymous NM_001330578.2:c.2781C>T NP_001317507.1:p.Asn927= synonymous NM_001330579.2:c.2763C>T NP_001317508.1:p.Asn921= synonymous NC_000013.11:g.51946329G>A NC_000013.10:g.52520465G>A NG_008806.1:g.70166C>T - Protein change
- -
- Other names
- -
- Canonical SPDI
- NC_000013.11:51946328:G:A
-
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.
-
0.00319 (A)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
The Genome Aggregation Database (gnomAD), exomes 0.00096
Exome Aggregation Consortium (ExAC) 0.00203
1000 Genomes Project 0.00319
1000 Genomes Project 30x 0.00344
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00365
The Genome Aggregation Database (gnomAD) 0.00430
Trans-Omics for Precision Medicine (TOPMed) 0.00445
- 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 |
2918 | 3062 | |
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 (5) |
criteria provided, multiple submitters, no conflicts
|
Jul 6, 2017 | RCV000252488.27 | |
| Benign (3) |
criteria provided, multiple submitters, no conflicts
|
Feb 5, 2024 | RCV000631255.20 | |
| Benign (3) |
criteria provided, multiple submitters, no conflicts
|
Oct 1, 2023 | RCV001537840.21 | |
| Likely benign (1) |
criteria provided, single submitter
|
Jun 22, 2022 | RCV002433473.9 |
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: SCV000301711.1
First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016 |
|
|
|
Benign
(Dec 02, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000602604.1
First in ClinVar: Sep 28, 2017 Last updated: Sep 28, 2017 |
|
|
|
Benign
(Aug 29, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000517796.4
First in ClinVar: Mar 08, 2017 Last updated: Jul 24, 2021 |
|
|
|
Benign
(Jul 06, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000694435.3
First in ClinVar: Mar 17, 2018 Last updated: Dec 11, 2022 |
Comment:
Variant summary: The c.3015C>T (p.Asn1005=) in ATP7B gene is a synonymous change that involves a non-conserved nucleotide. 5/5 programs in Alamut predict that this variant … (more)
Variant summary: The c.3015C>T (p.Asn1005=) in ATP7B gene is a synonymous change that involves a non-conserved nucleotide. 5/5 programs in Alamut predict that this variant does not affect normal splicing, however no functional studies supporting this notion were published at the time of evaluation. The variant is present in the control population dataset of ExAC at frequency of 0.0020 (123/60690 chrs tested), predominantly in individuals of African origin (0.02; 110/5328 chrs, including 2 homozygous occurrences). The observed frequency exceeds the maximum expected allele frequency for a pathogenic variant in this gene (0.0054), suggesting that it is a benign polymorphism. The variant was identified in at least 1 HBOC pt without strong evidence for causality. The variant of interest has not, to our knowledge, been identified in affected individuals via published reports, but is cited as Benign/Likely Benign by reputable database/clinical laboratories. Taken together, based on the prevalence in general population the variant was classified as Benign. (less)
|
|
|
Benign
(Aug 05, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Wilson disease
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV004362474.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
|
|
|
Benign
(Jan 31, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Wilson disease
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000752281.6
First in ClinVar: May 28, 2018 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: SCV004845432.1
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: 244
|
|
|
Likely benign
(Jun 22, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Inborn genetic diseases
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV002753357.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of … (more)
This alteration is classified as likely 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
(-)
|
criteria provided, single submitter
Method: not provided
|
not provided
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
|
Breakthrough Genomics, Breakthrough Genomics
Accession: SCV005230366.1
First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024 |
|
|
|
Benign
(Oct 01, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV004133155.10
First in ClinVar: Nov 20, 2023 Last updated: Oct 20, 2024 |
Comment:
ATP7B: BP4, BP7, BS1, BS2
Number of individuals with the variant: 1
|
|
|
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: SCV002034419.1 First in ClinVar: Dec 18, 2021 Last updated: Dec 18, 2021 |
|
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV002034912.1 First in ClinVar: Dec 18, 2021 Last updated: Dec 18, 2021 |
|
|
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Comment:
Comment:
This alteration is classified as likely 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:
ATP7B: BP4, BP7, BS1, BS2
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:
Variant summary: The c.3015C>T (p.Asn1005=) in ATP7B gene is a synonymous change that involves a non-conserved nucleotide. 5/5 programs in Alamut predict that this variant does not affect normal splicing, however no functional studies supporting this notion were published at the time of evaluation. The variant is present in the control population dataset of ExAC at frequency of 0.0020 (123/60690 chrs tested), predominantly in individuals of African origin (0.02; 110/5328 chrs, including 2 homozygous occurrences). The observed frequency exceeds the maximum expected allele frequency for a pathogenic variant in this gene (0.0054), suggesting that it is a benign polymorphism. The variant was identified in at least 1 HBOC pt without strong evidence for causality. The variant of interest has not, to our knowledge, been identified in affected individuals via published reports, but is cited as Benign/Likely Benign by reputable database/clinical laboratories. Taken together, based on the prevalence in general population the variant was classified as Benign.
Comment:
This alteration is classified as likely 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:
ATP7B: BP4, BP7, BS1, BS2
Citations for germline classification of this variant
Help| There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for rs74085888 ...
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 10, 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.