2-70942575-C-T

Position:

• chr2-70942575-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000234396.10(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 ENST00000234396.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.428

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-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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP6V1B1	NM_001692.4	c.119-1083C>T		intron_variant		ENST00000234396.10	NP_001683.2
ATP6V1B1-AS1	NR_110274.1	n.386-142G>A		intron_variant, non_coding_transcript_variant
ATP6V1B1-AS1	NR_110273.1	n.524-142G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP6V1B1	ENST00000234396.10	c.119-1083C>T		intron_variant		1	NM_001692.4	ENSP00000234396	P1
ATP6V1B1-AS1	ENST00000422761.1	n.523-142G>A		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR exome AF: 0.613

Gnomad4 AMR exome AF: 0.796

Gnomad4 ASJ exome AF: 0.774

Gnomad4 EAS exome AF: 0.810

Gnomad4 SAS exome AF: 0.841

Gnomad4 FIN exome AF: 0.701

Gnomad4 NFE exome AF: 0.709

Gnomad4 OTH exome AF: 0.736

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

Gnomad4 AFR AF: 0.603

Gnomad4 AMR AF: 0.786

Gnomad4 ASJ AF: 0.774

Gnomad4 EAS AF: 0.832

Gnomad4 SAS AF: 0.828

Gnomad4 FIN AF: 0.684

Gnomad4 NFE AF: 0.710

Gnomad4 OTH AF: 0.735

Alfa AF: 0.714 Hom.: 45515

Bravo AF: 0.696

Asia WGS AF: 0.826 AC: 2873 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.38
DANN	Benign	0.60

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

Publications

LitVar

Other links and lift over

dbSNP: rs2266917; hg19: chr2-71169705;