rs55655347

Variant names:

• chr2-70935800-A-G
• rs55655347
• ENST00000432367.6:n.*46-7858A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-70935800-A-G
• chr2-70935800-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000432367.6(VAX2):​n.*46-7858A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 599,784 control chromosomes in the GnomAD database, including 23,620 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (5188 hom., cov: 31)
  • Exomes 𝑓: 0.28 (18432 hom.)
• Consequence: VAX2 ENST00000432367.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.105
• Publications: 4 publications found

Genes affected

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]

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 Gene-Disease associations (from GenCC):

• renal tubular acidosis, distal, 2, with progressive sensorineural hearing loss

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia, G2P, ClinGen
• autosomal recessive distal renal tubular acidosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 2-70935800-A-G is Benign according to our data. Variant chr2-70935800-A-G is described in ClinVar as Benign. ClinVar VariationId is 1221522.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP6V1B1	NM_001692.4	c.-155A>G		upstream_gene_variant		ENST00000234396.10	NP_001683.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP6V1B1	ENST00000234396.10	c.-155A>G		upstream_gene_variant		1	NM_001692.4	ENSP00000234396.4

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38280 AN: 151732 Hom.: 5184 Cov.: 31

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.354

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.239

GnomAD4 exome AF: 0.276 AC: 123457 AN: 447936 Hom.: 18432 AF XY: 0.268 AC XY: 62545 AN XY: 233262

African (AFR) AF: 0.186 AC: 2190 AN: 11788

American (AMR) AF: 0.182 AC: 3165 AN: 17436

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 3114 AN: 13010

East Asian (EAS) AF: 0.180 AC: 5224 AN: 28966

South Asian (SAS) AF: 0.137 AC: 5500 AN: 40210

European-Finnish (FIN) AF: 0.343 AC: 13758 AN: 40148

Middle Eastern (MID) AF: 0.186 AC: 364 AN: 1954

European-Non Finnish (NFE) AF: 0.311 AC: 83632 AN: 269104

Other (OTH) AF: 0.257 AC: 6510 AN: 25320

GnomAD4 genome AF: 0.252 AC: 38291 AN: 151848 Hom.: 5188 Cov.: 31 AF XY: 0.252 AC XY: 18680 AN XY: 74202

African (AFR) AF: 0.187 AC: 7724 AN: 41404

American (AMR) AF: 0.200 AC: 3052 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 838 AN: 3468

East Asian (EAS) AF: 0.150 AC: 770 AN: 5148

South Asian (SAS) AF: 0.125 AC: 601 AN: 4804

European-Finnish (FIN) AF: 0.354 AC: 3734 AN: 10548

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.304 AC: 20659 AN: 67878

Other (OTH) AF: 0.236 AC: 497 AN: 2110

Alfa AF: 0.179 Hom.: 411

Bravo AF: 0.240

Asia WGS AF: 0.142 AC: 492 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	9.9
DANN	Benign	0.86
PhyloP100		0.10
PromoterAI		0.14	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs55655347; hg19: chr2-71162930; COSMIC: COSV107240029;