2-70935921-C-T

Position:

chr2-70935921-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001692.4(ATP6V1B1):c.-34C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 1,587,016 control chromosomes in the GnomAD database, including 10,033 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1266 hom., cov: 32)

Exomes 𝑓: 0.10 ( 8767 hom. )

Consequence

ATP6V1B1
NM_001692.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.0660

Variant links:

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]

ATP6V1B1 links:

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]

VAX2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 2-70935921-C-T is Benign according to our data. Variant chr2-70935921-C-T is described in ClinVar as [Benign]. Clinvar id is 336915.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-70935921-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP6V1B1	NM_001692.4 link	c.-34C>T		5_prime_UTR_variant	1/14	ENST00000234396.10	NP_001683.2	P15313

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP6V1B1	ENST00000234396 link	c.-34C>T		5_prime_UTR_variant	1/14	1	NM_001692.4	ENSP00000234396.4		P15313

Frequencies

GnomAD3 genomes

AF:

0.118

AC:

18015

AN:

152028

Hom.:

1264

Cov.:

show subpopulations

Gnomad AFR

AF:

0.160

Gnomad AMI

AF:

0.114

Gnomad AMR

AF:

0.0781

Gnomad ASJ

AF:

0.119

Gnomad EAS

AF:

0.226

Gnomad SAS

AF:

0.198

Gnomad FIN

AF:

0.108

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.0904

Gnomad OTH

AF:

0.112

GnomAD3 exomes

AF:

0.118

AC:

28598

AN:

243080

Hom.:

2219

AF XY:

0.122

AC XY:

16052

AN XY:

131556

show subpopulations

Gnomad AFR exome

AF:

0.164

Gnomad AMR exome

AF:

0.0569

Gnomad ASJ exome

AF:

0.117

Gnomad EAS exome

AF:

0.245

Gnomad SAS exome

AF:

0.207

Gnomad FIN exome

AF:

0.106

Gnomad NFE exome

AF:

0.0875

Gnomad OTH exome

AF:

0.107

GnomAD4 exome

AF:

0.102

AC:

146216

AN:

1434870

Hom.:

8767

Cov.:

AF XY:

0.105

AC XY:

74776

AN XY:

713062

show subpopulations

Gnomad4 AFR exome

AF:

0.165

Gnomad4 AMR exome

AF:

0.0587

Gnomad4 ASJ exome

AF:

0.120

Gnomad4 EAS exome

AF:

0.197

Gnomad4 SAS exome

AF:

0.203

Gnomad4 FIN exome

AF:

0.106

Gnomad4 NFE exome

AF:

0.0890

Gnomad4 OTH exome

AF:

0.117

GnomAD4 genome

AF:

0.118

AC:

18028

AN:

152146

Hom.:

1266

Cov.:

AF XY:

0.122

AC XY:

9086

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.160

Gnomad4 AMR

AF:

0.0780

Gnomad4 ASJ

AF:

0.119

Gnomad4 EAS

AF:

0.225

Gnomad4 SAS

AF:

0.200

Gnomad4 FIN

AF:

0.108

Gnomad4 NFE

AF:

0.0904

Gnomad4 OTH

AF:

0.111

Alfa

AF:

0.0990

Hom.:

190

Bravo

AF:

0.114

Asia WGS

AF:

0.184

AC:

639

AN:

3478

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	Illumina Laboratory Services, Illumina	Jan 12, 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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 10, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 09, 2017

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. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

6.4

DANN

Benign

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over