rs77794859
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001692.4(ATP6V1B1):c.*12G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00504 in 1,606,664 control chromosomes in the GnomAD database, including 355 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.026 ( 173 hom., cov: 31)
Exomes 𝑓: 0.0028 ( 182 hom. )
Consequence
ATP6V1B1
NM_001692.4 3_prime_UTR
NM_001692.4 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.96
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.71).
BP6
?
Variant 2-70965133-G-A is Benign according to our data. Variant chr2-70965133-G-A is described in ClinVar as [Benign]. Clinvar id is 44220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-70965133-G-A is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0898 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATP6V1B1 | NM_001692.4 | c.*12G>A | 3_prime_UTR_variant | 14/14 | ENST00000234396.10 | ||
ATP6V1B1 | XM_011532907.3 | c.*12G>A | 3_prime_UTR_variant | 13/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATP6V1B1 | ENST00000234396.10 | c.*12G>A | 3_prime_UTR_variant | 14/14 | 1 | NM_001692.4 | P1 | ||
ATP6V1B1 | ENST00000412314.5 | c.*12G>A | 3_prime_UTR_variant | 14/14 | 5 | ||||
VAX2 | ENST00000432367.6 | c.*1330G>A | 3_prime_UTR_variant, NMD_transcript_variant | 15/15 | 5 | ||||
ATP6V1B1 | ENST00000433895.2 | downstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0262 AC: 3981AN: 152094Hom.: 171 Cov.: 31
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GnomAD3 exomes AF: 0.00665 AC: 1599AN: 240542Hom.: 81 AF XY: 0.00530 AC XY: 700AN XY: 132074
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GnomAD4 exome AF: 0.00281 AC: 4091AN: 1454452Hom.: 182 Cov.: 33 AF XY: 0.00241 AC XY: 1747AN XY: 723906
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GnomAD4 genome ? AF: 0.0263 AC: 4001AN: 152212Hom.: 173 Cov.: 31 AF XY: 0.0260 AC XY: 1938AN XY: 74410
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Renal tubular acidosis with progressive nerve deafness Benign:2
Benign, criteria provided, single submitter | clinical testing | Counsyl | Mar 06, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | 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. - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 07, 2012 | *12G>A in Exon 14 of ATP6V1B1: This variant is not expected to have clinical sig nificance because it has been identified in 8.1% (301/3718) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http: //evs.gs.washington.edu/EVS; dbSNP rs77794859). - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 11, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at