chr2-70943438-C-T

Variant names:

• chr2-70943438-C-T
• rs75946270
• NM_001692.4:c.119-220C>T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001692.4(ATP6V1B1):​c.119-220C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0101 in 677,934 control chromosomes in the GnomAD database, including 287 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.029 (212 hom., cov: 33)
  • Exomes 𝑓: 0.0046 (75 hom.)
• Consequence: ATP6V1B1 NM_001692.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.50

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

Verdict is Benign. Variant got -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BP6: Variant 2-70943438-C-T is Benign according to our data. Variant chr2-70943438-C-T is described in ClinVar as [Benign]. Clinvar id is 1247280.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0947 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP6V1B1	NM_001692.4	c.119-220C>T		intron_variant	Intron 1 of 13	ENST00000234396.10	NP_001683.2
ATP6V1B1-AS1	NR_110273.1	n.524-1005G>A		intron_variant	Intron 2 of 2
ATP6V1B1-AS1	NR_110274.1	n.386-1005G>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP6V1B1	ENST00000234396.10	c.119-220C>T		intron_variant	Intron 1 of 13	1	NM_001692.4	ENSP00000234396.4
ENSG00000258881	ENST00000606025.5	c.476-1005G>A		intron_variant	Intron 5 of 5	5		ENSP00000475641.1

Frequencies

GnomAD3 genomes AF: 0.0290 AC: 4418 AN: 152128 Hom.: 212 Cov.: 33

Gnomad AFR AF: 0.0973

Gnomad AMI AF: 0.0275

Gnomad AMR AF: 0.0150

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00109

Gnomad OTH AF: 0.0249

GnomAD4 exome AF: 0.00461 AC: 2421 AN: 525688 Hom.: 75 Cov.: 4 AF XY: 0.00369 AC XY: 1042 AN XY: 282754

Gnomad4 AFR exome AF: 0.0969

Gnomad4 AMR exome AF: 0.00823

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000241

Gnomad4 FIN exome AF: 0.0000307

Gnomad4 NFE exome AF: 0.000971

Gnomad4 OTH exome AF: 0.00978

GnomAD4 genome AF: 0.0291 AC: 4429 AN: 152246 Hom.: 212 Cov.: 33 AF XY: 0.0277 AC XY: 2062 AN XY: 74454

Gnomad4 AFR AF: 0.0972

Gnomad4 AMR AF: 0.0150

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00109

Gnomad4 OTH AF: 0.0246

Alfa AF: 0.000273 Hom.: 0

Bravo AF: 0.0324

Asia WGS AF: 0.00779 AC: 27 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 23, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	18
DANN	Benign	0.94

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: rs75946270; hg19: chr2-71170568;