NM_001692.4:c.119-119C>T

Variant names:

• chr2-70943539-C-T
• rs17040279
• NM_001692.4:c.119-119C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001692.4(ATP6V1B1):​c.119-119C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0011 in 1,078,160 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0045 (4 hom., cov: 33)
  • Exomes 𝑓: 0.00055 (4 hom.)
• Consequence: ATP6V1B1 NM_001692.4 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.07
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 2-70943539-C-T is Benign according to our data. Variant chr2-70943539-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1191804.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00449 (682/152036) while in subpopulation AFR AF = 0.0157 (650/41400). AF 95% confidence interval is 0.0147. There are 4 homozygotes in GnomAd4. There are 333 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 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.119-119C>T		intron	N/A	NP_001683.2
	ATP6V1B1-AS1	NR_110273.1		n.524-1106G>A		intron	N/A
	ATP6V1B1-AS1	NR_110274.1		n.386-1106G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP6V1B1	ENST00000234396.10	TSL:1 MANE Select	c.119-119C>T		intron	N/A	ENSP00000234396.4	P15313
	ENSG00000258881	ENST00000606025.5	TSL:5	c.476-1106G>A		intron	N/A	ENSP00000475641.1	U3KQ87
	ATP6V1B1	ENST00000872157.1		c.119-119C>T		intron	N/A	ENSP00000542216.1

Frequencies

GnomAD3 genomes AF: 0.00449 AC: 682 AN: 151916 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.0157

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000883

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.00101 AC: 161 AN: 159252 AF XY: 0.000763

Gnomad AFR exome AF: 0.0142

Gnomad AMR exome AF: 0.000828

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000460

Gnomad OTH exome AF: 0.000873

GnomAD4 exome AF: 0.000545 AC: 505 AN: 926124 Hom.: 4 Cov.: 13 AF XY: 0.000428 AC XY: 204 AN XY: 476494

African (AFR) AF: 0.0152 AC: 348 AN: 22924

American (AMR) AF: 0.000953 AC: 34 AN: 35684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22262

East Asian (EAS) AF: 0.00 AC: 0 AN: 33628

South Asian (SAS) AF: 0.000113 AC: 8 AN: 70506

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42026

Middle Eastern (MID) AF: 0.000210 AC: 1 AN: 4764

European-Non Finnish (NFE) AF: 0.0000660 AC: 43 AN: 651718

Other (OTH) AF: 0.00167 AC: 71 AN: 42612

GnomAD4 genome AF: 0.00449 AC: 682 AN: 152036 Hom.: 4 Cov.: 33 AF XY: 0.00448 AC XY: 333 AN XY: 74342

African (AFR) AF: 0.0157 AC: 650 AN: 41400

American (AMR) AF: 0.00144 AC: 22 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5146

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000883 AC: 6 AN: 67980

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.00120 Hom.: 1

Bravo AF: 0.00505

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	9.1
DANN	Benign	0.74
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism

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: rs17040279; hg19: chr2-71170669;