2-70942575-C-T

Variant names:

• chr2-70942575-C-T
• rs2266917
• NM_001692.4:c.119-1083C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001692.4(ATP6V1B1):​c.119-1083C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.713 in 394,354 control chromosomes in the GnomAD database, including 100,878 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.70 (37243 hom., cov: 32)
  • Exomes 𝑓: 0.72 (63635 hom.)
• Consequence: ATP6V1B1 NM_001692.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.428
• Publications: 8 publications found

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]

ENSG00000258881 (HGNC:):

ATP6V1B1-AS1 (HGNC:51118): (ATP6V1B1 antisense RNA 1)

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.812 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001692.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP6V1B1	NM_001692.4	MANE Select	c.119-1083C>T		intron	N/A	NP_001683.2
	ATP6V1B1-AS1	NR_110273.1		n.524-142G>A		intron	N/A
	ATP6V1B1-AS1	NR_110274.1		n.386-142G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP6V1B1	ENST00000234396.10	TSL:1 MANE Select	c.119-1083C>T		intron	N/A	ENSP00000234396.4
	ENSG00000258881	ENST00000606025.5	TSL:5	c.476-142G>A		intron	N/A	ENSP00000475641.1
	ATP6V1B1	ENST00000412314.5	TSL:5	c.119-1083C>T		intron	N/A	ENSP00000388353.1

Frequencies

GnomAD3 genomes AF: 0.696 AC: 105842 AN: 152030 Hom.: 37211 Cov.: 32

Gnomad AFR AF: 0.603

Gnomad AMI AF: 0.646

Gnomad AMR AF: 0.786

Gnomad ASJ AF: 0.774

Gnomad EAS AF: 0.832

Gnomad SAS AF: 0.828

Gnomad FIN AF: 0.684

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.710

Gnomad OTH AF: 0.732

GnomAD4 exome AF: 0.723 AC: 175177 AN: 242206 Hom.: 63635 AF XY: 0.725 AC XY: 89026 AN XY: 122792

African (AFR) AF: 0.613 AC: 4350 AN: 7094

American (AMR) AF: 0.796 AC: 5830 AN: 7322

Ashkenazi Jewish (ASJ) AF: 0.774 AC: 7079 AN: 9148

East Asian (EAS) AF: 0.810 AC: 18389 AN: 22696

South Asian (SAS) AF: 0.841 AC: 1819 AN: 2164

European-Finnish (FIN) AF: 0.701 AC: 14250 AN: 20336

Middle Eastern (MID) AF: 0.795 AC: 1017 AN: 1280

European-Non Finnish (NFE) AF: 0.709 AC: 110547 AN: 155992

Other (OTH) AF: 0.736 AC: 11896 AN: 16174

GnomAD4 genome AF: 0.696 AC: 105913 AN: 152148 Hom.: 37243 Cov.: 32 AF XY: 0.698 AC XY: 51925 AN XY: 74372

African (AFR) AF: 0.603 AC: 25026 AN: 41498

American (AMR) AF: 0.786 AC: 12031 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.774 AC: 2687 AN: 3470

East Asian (EAS) AF: 0.832 AC: 4300 AN: 5166

South Asian (SAS) AF: 0.828 AC: 3996 AN: 4826

European-Finnish (FIN) AF: 0.684 AC: 7226 AN: 10572

Middle Eastern (MID) AF: 0.823 AC: 242 AN: 294

European-Non Finnish (NFE) AF: 0.710 AC: 48263 AN: 68000

Other (OTH) AF: 0.735 AC: 1553 AN: 2112

Alfa AF: 0.710 Hom.: 66257

Bravo AF: 0.696

Asia WGS AF: 0.826 AC: 2873 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.38
DANN	Benign	0.60
PhyloP100		-0.43
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2266917; hg19: chr2-71169705;