ClinVar Genomic variation as it relates to human health
NM_001692.4(ATP6V1B1):c.1394G>A (p.Arg465His)
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(1); Benign(8); Likely benign(1)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001692.4(ATP6V1B1):c.1394G>A (p.Arg465His)
Variation ID: 178290 Accession: VCV000178290.26
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 2p13.3 2: 70964973 (GRCh38) [ NCBI UCSC ] 2: 71192103 (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 Feb 14, 2024 Jan 31, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001692.4:c.1394G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001683.2:p.Arg465His missense NC_000002.12:g.70964973G>A NC_000002.11:g.71192103G>A NG_008016.1:g.34106G>A LRG_1176:g.34106G>A LRG_1176t1:c.1394G>A LRG_1176p1:p.Arg465His P15313:p.Arg465His - Protein change
- R465H
- Other names
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- Canonical SPDI
- NC_000002.12:70964972: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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0.00619 (A)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD), exomes 0.00301
Exome Aggregation Consortium (ExAC) 0.00346
1000 Genomes Project 30x 0.00593
1000 Genomes Project 0.00619
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00254
The Genome Aggregation Database (gnomAD) 0.00275
Trans-Omics for Precision Medicine (TOPMed) 0.00277
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
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. |
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ATP6V1B1 | - | - |
GRCh38 GRCh37 |
619 | 680 |
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 (3) |
criteria provided, multiple submitters, no conflicts
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Dec 10, 2021 | RCV000155034.9 | |
Conflicting interpretations of pathogenicity (6) |
criteria provided, conflicting classifications
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Jul 22, 2021 | RCV000490321.13 | |
Benign (2) |
criteria provided, multiple submitters, no conflicts
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Jan 31, 2024 | RCV000885591.10 |
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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Uncertain significance
(Mar 18, 2016)
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criteria provided, single submitter
Method: reference population
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Renal tubular acidosis with progressive nerve deafness
Affected status: unknown
Allele origin:
germline
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Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center
Accession: SCV000267215.1
First in ClinVar: May 25, 2017 Last updated: May 25, 2017 |
Number of individuals with the variant: 1
Age: 40-69 years
Ethnicity/Population group: East Asian
Geographic origin: South Korean
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Benign
(Jan 22, 2015)
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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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Eurofins Ntd Llc (ga)
Accession: SCV000226078.5
First in ClinVar: Jun 28, 2015 Last updated: Jun 28, 2015 |
Number of individuals with the variant: 2
Sex: mixed
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Benign
(Apr 30, 2012)
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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: SCV000204718.4
First in ClinVar: Jan 31, 2015 Last updated: Jun 28, 2015 |
Comment:
Arg465His in Exon 14 of ATP6V1B1: This variant is not expected to have clinical significance because it has been identified in 0.8% (30/3738) of African … (more)
Arg465His in Exon 14 of ATP6V1B1: This variant is not expected to have clinical significance because it has been identified in 0.8% (30/3738) of African America n chromosomes from a broad population by the NHLBI Exome Sequencing Project (htt p://evs.gs.washington.edu/EVS; dbSNP rs142905621). (less)
Number of individuals with the variant: 7
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Benign
(Apr 27, 2017)
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criteria provided, single submitter
Method: clinical testing
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Renal tubular acidosis with progressive nerve deafness
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001297287.1
First in ClinVar: May 31, 2020 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 was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. (less)
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Benign
(-)
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criteria provided, single submitter
Method: research
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Renal tubular acidosis with progressive nerve deafness
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard
Accession: SCV001435181.1
First in ClinVar: Oct 03, 2020 Last updated: Oct 03, 2020 |
Comment:
The heterozygous p.Arg465His variant in ATP6V1B1 has been identified in a German individual with renal tubular acidosis and no other potentially causal variant identified in … (more)
The heterozygous p.Arg465His variant in ATP6V1B1 has been identified in a German individual with renal tubular acidosis and no other potentially causal variant identified in the gene (PMID: 12579397), but has also been identified in >1% of South Asian chromosomes and 6 homozygotes by ExAC (http://gnomad.broadinstitute.org/). In summary, this variant meets criteria to be classified as benign for autosomal recessive renal tubular acidosis. (less)
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Benign
(May 18, 2021)
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criteria provided, single submitter
Method: clinical testing
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Renal tubular acidosis with progressive nerve deafness
Affected status: no
Allele origin:
germline
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Pars Genome Lab
Accession: SCV001736797.1
First in ClinVar: Jun 19, 2021 Last updated: Jun 19, 2021 |
Sex: mixed
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Likely benign
(Dec 10, 2021)
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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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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV002050929.1
First in ClinVar: Jan 08, 2022 Last updated: Jan 08, 2022 |
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Benign
(Jul 19, 2018)
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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: SCV001950641.2
First in ClinVar: Oct 02, 2021 Last updated: Mar 04, 2023 |
Comment:
This variant is associated with the following publications: (PMID: 27535533, 12579397, 26920127)
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Benign
(Jul 22, 2021)
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criteria provided, single submitter
Method: clinical testing
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Renal tubular acidosis with progressive nerve deafness
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV001810282.1
First in ClinVar: Sep 08, 2021 Last updated: Sep 08, 2021 |
Sex: mixed
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Benign
(Jan 31, 2024)
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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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Invitae
Accession: SCV001029050.6
First in ClinVar: Dec 17, 2019 Last updated: Feb 14, 2024 |
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Benign
(Sep 16, 2020)
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no assertion criteria provided
Method: clinical testing
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Renal tubular acidosis with progressive nerve deafness
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV001457591.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 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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Confirmation of the ATP6B1 gene as responsible for distal renal tubular acidosis. | Ruf R | Pediatric nephrology (Berlin, Germany) | 2003 | PMID: 12579397 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=ATP6V1B1 | - | - | - | - |
Text-mined citations for rs142905621 ...
HelpRecord last updated Mar 30, 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.