2-70943568-GGA-G

Variant names:

• chr2-70943568-GGA-G
• rs111644218
• NM_001692.4:c.119-84_119-83delAG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001692.4(ATP6V1B1):​c.119-84_119-83delAG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0198 in 1,358,340 control chromosomes in the GnomAD database, including 1,299 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.056 (678 hom., cov: 32)
  • Exomes 𝑓: 0.015 (621 hom.)
• Consequence: ATP6V1B1 NM_001692.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00
• Publications: 1 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 2-70943568-GGA-G is Benign according to our data. Variant chr2-70943568-GGA-G is described in ClinVar as Benign. ClinVar VariationId is 1274062.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.17 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP6V1B1	NM_001692.4	MANE Select	c.119-84_119-83delAG		intron	N/A	NP_001683.2
	ATP6V1B1-AS1	NR_110273.1		n.524-1137_524-1136delTC		intron	N/A
	ATP6V1B1-AS1	NR_110274.1		n.386-1137_386-1136delTC		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP6V1B1	ENST00000234396.10	TSL:1 MANE Select	c.119-84_119-83delAG		intron	N/A	ENSP00000234396.4	P15313
	ENSG00000258881	ENST00000606025.5	TSL:5	c.476-1137_476-1136delTC		intron	N/A	ENSP00000475641.1	U3KQ87
	ATP6V1B1	ENST00000872157.1		c.119-84_119-83delAG		intron	N/A	ENSP00000542216.1

Frequencies

GnomAD3 genomes AF: 0.0561 AC: 8534 AN: 152006 Hom.: 675 Cov.: 32

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0310

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00684

Gnomad FIN AF: 0.00414

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0110

Gnomad OTH AF: 0.0383

GnomAD2 exomes AF: 0.0203 AC: 4097 AN: 202290 AF XY: 0.0170

Gnomad AFR exome AF: 0.175

Gnomad AMR exome AF: 0.0141

Gnomad ASJ exome AF: 0.000108

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00487

Gnomad NFE exome AF: 0.0124

Gnomad OTH exome AF: 0.0143

GnomAD4 exome AF: 0.0152 AC: 18305 AN: 1206216 Hom.: 621 AF XY: 0.0143 AC XY: 8697 AN XY: 609524

African (AFR) AF: 0.174 AC: 4948 AN: 28464

American (AMR) AF: 0.0152 AC: 606 AN: 39774

Ashkenazi Jewish (ASJ) AF: 0.0000413 AC: 1 AN: 24218

East Asian (EAS) AF: 0.00 AC: 0 AN: 36194

South Asian (SAS) AF: 0.00731 AC: 571 AN: 78108

European-Finnish (FIN) AF: 0.00448 AC: 218 AN: 48624

Middle Eastern (MID) AF: 0.00656 AC: 35 AN: 5334

European-Non Finnish (NFE) AF: 0.0122 AC: 10910 AN: 893708

Other (OTH) AF: 0.0196 AC: 1016 AN: 51792

GnomAD4 genome AF: 0.0563 AC: 8563 AN: 152124 Hom.: 678 Cov.: 32 AF XY: 0.0553 AC XY: 4113 AN XY: 74388

African (AFR) AF: 0.173 AC: 7182 AN: 41460

American (AMR) AF: 0.0309 AC: 473 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00684 AC: 33 AN: 4822

European-Finnish (FIN) AF: 0.00414 AC: 44 AN: 10620

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0110 AC: 749 AN: 67992

Other (OTH) AF: 0.0379 AC: 80 AN: 2110

Alfa AF: 0.0307 Hom.: 68

Bravo AF: 0.0634

Asia WGS AF: 0.0140 AC: 48 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: 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		0.0
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: rs111644218; hg19: chr2-71170698;