8-20224379-T-G

Position:

• chr8-20224379-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The variant allele was found at a frequency of 0.419 in 150,688 control chromosomes in the GnomAD database, including 15,114 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.42 (15114 hom., cov: 32)
• Consequence: intergenic_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.167

Genes affected

(HGNC:):

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.20224379T>G		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP6V1B2	ENST00000521442.1	n.101-903T>G		intron_variant		3		ENSP00000430866.2

Frequencies

GnomAD3 genomes AF: 0.418 AC: 62984 AN: 150564 Hom.: 15087 Cov.: 32

Gnomad AFR AF: 0.656

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.423

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.419 AC: 63064 AN: 150688 Hom.: 15114 Cov.: 32 AF XY: 0.410 AC XY: 30213 AN XY: 73652

Gnomad4 AFR AF: 0.656

Gnomad4 AMR AF: 0.430

Gnomad4 ASJ AF: 0.364

Gnomad4 EAS AF: 0.240

Gnomad4 SAS AF: 0.281

Gnomad4 FIN AF: 0.222

Gnomad4 NFE AF: 0.336

Gnomad4 OTH AF: 0.421

Alfa AF: 0.335 Hom.: 15770

Bravo AF: 0.444

Asia WGS AF: 0.277 AC: 965 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.23
DANN	Benign	0.47

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1390943; hg19: chr8-20081890;