rs76241121
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_001692.4(ATP6V1B1):c.785+10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000208 in 1,613,872 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00035 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00019 ( 2 hom. )
Consequence
ATP6V1B1
NM_001692.4 intron
NM_001692.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.608
Genes affected
ATP6V1B1 (HGNC:853): (ATPase H+ transporting V1 subunit B1) This gene encodes a component of vacuolar ATPase (V-ATPase), a multisubunit enzyme that mediates acidification of eukaryotic intracellular organelles. V-ATPase dependent organelle acidification is necessary for such intracellular processes as protein sorting, zymogen activation, receptor-mediated endocytosis, and synaptic vesicle proton gradient generation. V-ATPase is composed of a cytosolic V1 domain and a transmembrane V0 domain. The V1 domain consists of three A and three B subunits, two G subunits plus the C, D, E, F, and H subunits. The V1 domain contains the ATP catalytic site. The V0 domain consists of five different subunits: a, c, c', c'', and d. Additional isoforms of many of the V1 and V0 subunit proteins are encoded by multiple genes or alternatively spliced transcript variants. This encoded protein is one of two V1 domain B subunit isoforms and is found in the kidney. Mutations in this gene cause distal renal tubular acidosis associated with sensorineural deafness. [provided by RefSeq, Jul 2008]
VAX2 (HGNC:12661): (ventral anterior homeobox 2) This gene encodes a homeobox protein and is almost exclusively expressed in the ventral portion of the retina during development. In mouse studies, this gene was found to be required for the correct formation of the optic fissure and other aspects of retinal development. [provided by RefSeq, Sep 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
?
Variant 2-70961703-C-T is Benign according to our data. Variant chr2-70961703-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 226462.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
?
High Homozygotes in GnomAdExome4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATP6V1B1 | NM_001692.4 | c.785+10C>T | intron_variant | ENST00000234396.10 | |||
ATP6V1B1 | XM_011532907.3 | c.905+10C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATP6V1B1 | ENST00000234396.10 | c.785+10C>T | intron_variant | 1 | NM_001692.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000355 AC: 54AN: 152236Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000656 AC: 165AN: 251402Hom.: 2 AF XY: 0.000581 AC XY: 79AN XY: 135874
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GnomAD4 exome AF: 0.000193 AC: 282AN: 1461518Hom.: 2 Cov.: 31 AF XY: 0.000204 AC XY: 148AN XY: 727090
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GnomAD4 genome ? AF: 0.000354 AC: 54AN: 152354Hom.: 0 Cov.: 33 AF XY: 0.000376 AC XY: 28AN XY: 74494
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 14, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Aug 12, 2015 | c.785+10C>T in intron 08 of ATP6V1B1: This variant is not expected to have clini cal significance because it is not located within the conserved splice consensus sequence and has been identified in 0.8% (68/8644) of East Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNPrs 76241121). - |
Renal tubular acidosis with progressive nerve deafness Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Counsyl | Nov 26, 2017 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at