8-20209328-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001693.4(ATP6V1B2):c.193-105A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0393 in 1,120,450 control chromosomes in the GnomAD database, including 1,129 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.043 (162 hom., cov: 32)
  • Exomes 𝑓: 0.039 (967 hom.)
• Consequence: ATP6V1B2 NM_001693.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.21

Genes affected

ATP6V1B2 (HGNC:854): (ATPase H+ transporting V1 subunit B2) 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, three B, and two G subunits, as well as a C, D, E, F, and H subunit. The V1 domain contains the ATP catalytic site. The protein encoded by this gene is one of two V1 domain B subunit isoforms and is the only B isoform highly expressed in osteoclasts. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 8-20209328-A-G is Benign according to our data. Variant chr8-20209328-A-G is described in ClinVar as [Benign]. Clinvar id is 1252828.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP6V1B2	NM_001693.4	c.193-105A>G		intron_variant		ENST00000276390.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP6V1B2	ENST00000276390.7	c.193-105A>G		intron_variant		1	NM_001693.4	P1

Frequencies

GnomAD3 genomes AF: 0.0427 AC: 6496 AN: 152190 Hom.: 160 Cov.: 32

Gnomad AFR AF: 0.0550

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0622

Gnomad ASJ AF: 0.0245

Gnomad EAS AF: 0.0681

Gnomad SAS AF: 0.0462

Gnomad FIN AF: 0.0282

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0323

Gnomad OTH AF: 0.0396

GnomAD4 exome AF: 0.0387 AC: 37512 AN: 968142 Hom.: 967 AF XY: 0.0385 AC XY: 18904 AN XY: 491386

Gnomad4 AFR exome AF: 0.0527

Gnomad4 AMR exome AF: 0.0767

Gnomad4 ASJ exome AF: 0.0276

Gnomad4 EAS exome AF: 0.113

Gnomad4 SAS exome AF: 0.0487

Gnomad4 FIN exome AF: 0.0299

Gnomad4 NFE exome AF: 0.0330

Gnomad4 OTH exome AF: 0.0358

GnomAD4 genome AF: 0.0427 AC: 6499 AN: 152308 Hom.: 162 Cov.: 32 AF XY: 0.0428 AC XY: 3187 AN XY: 74474

Gnomad4 AFR AF: 0.0549

Gnomad4 AMR AF: 0.0626

Gnomad4 ASJ AF: 0.0245

Gnomad4 EAS AF: 0.0679

Gnomad4 SAS AF: 0.0456

Gnomad4 FIN AF: 0.0282

Gnomad4 NFE AF: 0.0323

Gnomad4 OTH AF: 0.0392

Alfa AF: 0.0317 Hom.: 69

Bravo AF: 0.0456

Asia WGS AF: 0.0520 AC: 183 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 16, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.063
Dann	Benign	0.44

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

Publications

LitVar

Other links and lift over

dbSNP: rs2291791; hg19: chr8-20066839;