chr8-20209366-A-C

Position:

• chr8-20209366-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001693.4(ATP6V1B2):​c.193-67A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0447 in 1,445,848 control chromosomes in the GnomAD database, including 1,722 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.034 (129 hom., cov: 32)
  • Exomes 𝑓: 0.046 (1593 hom.)
• Consequence: ATP6V1B2 NM_001693.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.40

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 8-20209366-A-C is Benign according to our data. Variant chr8-20209366-A-C is described in ClinVar as [Benign]. Clinvar id is 1262374.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP6V1B2	NM_001693.4	c.193-67A>C		intron_variant		ENST00000276390.7	NP_001684.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP6V1B2	ENST00000276390.7	c.193-67A>C		intron_variant		1	NM_001693.4	ENSP00000276390	P1

Frequencies

GnomAD3 genomes AF: 0.0345 AC: 5251 AN: 152110 Hom.: 129 Cov.: 32

Gnomad AFR AF: 0.0127

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.0326

Gnomad ASJ AF: 0.0655

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0133

Gnomad FIN AF: 0.0147

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0532

Gnomad OTH AF: 0.0401

GnomAD4 exome AF: 0.0459 AC: 59384 AN: 1293620 Hom.: 1593 AF XY: 0.0452 AC XY: 29383 AN XY: 650716

Gnomad4 AFR exome AF: 0.0106

Gnomad4 AMR exome AF: 0.0294

Gnomad4 ASJ exome AF: 0.0664

Gnomad4 EAS exome AF: 0.000106

Gnomad4 SAS exome AF: 0.0121

Gnomad4 FIN exome AF: 0.0188

Gnomad4 NFE exome AF: 0.0532

Gnomad4 OTH exome AF: 0.0461

GnomAD4 genome AF: 0.0345 AC: 5251 AN: 152228 Hom.: 129 Cov.: 32 AF XY: 0.0326 AC XY: 2430 AN XY: 74448

Gnomad4 AFR AF: 0.0126

Gnomad4 AMR AF: 0.0326

Gnomad4 ASJ AF: 0.0655

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0131

Gnomad4 FIN AF: 0.0147

Gnomad4 NFE AF: 0.0533

Gnomad4 OTH AF: 0.0402

Alfa AF: 0.0426 Hom.: 23

Bravo AF: 0.0356

Asia WGS AF: 0.00693 AC: 24 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 10, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.47
DANN	Benign	0.75

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: rs78680143; hg19: chr8-20066877;