2-70943438-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• 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 -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 VariationId 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.

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.119-220C>T		intron	N/A	NP_001683.2
	ATP6V1B1-AS1	NR_110273.1		n.524-1005G>A		intron	N/A
	ATP6V1B1-AS1	NR_110274.1		n.386-1005G>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.119-220C>T		intron	N/A	ENSP00000234396.4	P15313
	ENSG00000258881	ENST00000606025.5	TSL:5	c.476-1005G>A		intron	N/A	ENSP00000475641.1	U3KQ87
	ATP6V1B1	ENST00000872157.1		c.119-220C>T		intron	N/A	ENSP00000542216.1

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

African (AFR) AF: 0.0969 AC: 1498 AN: 15462

American (AMR) AF: 0.00823 AC: 277 AN: 33640

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18332

East Asian (EAS) AF: 0.00 AC: 0 AN: 31572

South Asian (SAS) AF: 0.000241 AC: 14 AN: 58128

European-Finnish (FIN) AF: 0.0000307 AC: 1 AN: 32530

Middle Eastern (MID) AF: 0.0163 AC: 49 AN: 3014

European-Non Finnish (NFE) AF: 0.000971 AC: 295 AN: 303668

Other (OTH) AF: 0.00978 AC: 287 AN: 29342

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

African (AFR) AF: 0.0972 AC: 4039 AN: 41540

American (AMR) AF: 0.0150 AC: 229 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5166

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.00109 AC: 74 AN: 68000

Other (OTH) AF: 0.0246 AC: 52 AN: 2112

Alfa AF: 0.000273 Hom.: 0

Bravo AF: 0.0324

Asia WGS AF: 0.00779 AC: 27 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: 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	-0.28
CADD	Benign	18
DANN	Benign	0.94
PhyloP100		1.5
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: rs75946270; hg19: chr2-71170568;