NM_001692.4:c.119-257_119-256insAG

Variant names:

• chr2-70943401-C-CAG
• rs782603378
• NM_001692.4:c.119-257_119-256insAG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001692.4(ATP6V1B1):​c.119-257_119-256insAG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.028 in 625,966 control chromosomes in the GnomAD database, including 308 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.024 (45 hom., cov: 32)
  • Exomes 𝑓: 0.029 (263 hom.)
• Consequence: ATP6V1B1 NM_001692.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.623
• Publications: 0 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 -10 ACMG points.

• BP6: Variant 2-70943401-C-CAG is Benign according to our data. Variant chr2-70943401-C-CAG is described in ClinVar as Likely_benign. ClinVar VariationId is 1211479.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.024 (3650/152226) while in subpopulation NFE AF = 0.0355 (2412/67978). AF 95% confidence interval is 0.0343. There are 45 homozygotes in GnomAd4. There are 1766 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 45 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP6V1B1	NM_001692.4	MANE Select	c.119-257_119-256insAG		intron	N/A	NP_001683.2
	ATP6V1B1-AS1	NR_110273.1		n.524-969_524-968insCT		intron	N/A
	ATP6V1B1-AS1	NR_110274.1		n.386-969_386-968insCT		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP6V1B1	ENST00000234396.10	TSL:1 MANE Select	c.119-257_119-256insAG		intron	N/A	ENSP00000234396.4	P15313
	ENSG00000258881	ENST00000606025.5	TSL:5	c.476-969_476-968insCT		intron	N/A	ENSP00000475641.1	U3KQ87
	ATP6V1B1	ENST00000872157.1		c.119-257_119-256insAG		intron	N/A	ENSP00000542216.1

Frequencies

GnomAD3 genomes AF: 0.0240 AC: 3651 AN: 152108 Hom.: 45 Cov.: 32

Gnomad AFR AF: 0.00623

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0231

Gnomad ASJ AF: 0.0124

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0230

Gnomad FIN AF: 0.0396

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0355

Gnomad OTH AF: 0.0110

GnomAD4 exome AF: 0.0293 AC: 13873 AN: 473740 Hom.: 263 Cov.: 0 AF XY: 0.0293 AC XY: 7371 AN XY: 251960

African (AFR) AF: 0.00558 AC: 79 AN: 14152

American (AMR) AF: 0.0302 AC: 858 AN: 28444

Ashkenazi Jewish (ASJ) AF: 0.0101 AC: 154 AN: 15298

East Asian (EAS) AF: 0.000856 AC: 26 AN: 30378

South Asian (SAS) AF: 0.0318 AC: 1645 AN: 51652

European-Finnish (FIN) AF: 0.0424 AC: 1254 AN: 29560

Middle Eastern (MID) AF: 0.0145 AC: 31 AN: 2140

European-Non Finnish (NFE) AF: 0.0331 AC: 9107 AN: 275248

Other (OTH) AF: 0.0268 AC: 719 AN: 26868

GnomAD4 genome AF: 0.0240 AC: 3650 AN: 152226 Hom.: 45 Cov.: 32 AF XY: 0.0237 AC XY: 1766 AN XY: 74434

African (AFR) AF: 0.00621 AC: 258 AN: 41548

American (AMR) AF: 0.0231 AC: 353 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0124 AC: 43 AN: 3462

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5176

South Asian (SAS) AF: 0.0228 AC: 110 AN: 4826

European-Finnish (FIN) AF: 0.0396 AC: 421 AN: 10620

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0355 AC: 2412 AN: 67978

Other (OTH) AF: 0.0109 AC: 23 AN: 2114

Alfa AF: 0.0427 Hom.: 5

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.62
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: rs782603378; hg19: chr2-71170531;