8-20224379-T-G

Variant names:

• chr8-20224379-T-G
• rs1390943
• ENST00000521442.1:n.101-903T>G

Variant summary

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

The ENST00000521442.1(ATP6V1B2):​n.101-903T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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: ATP6V1B2 ENST00000521442.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.167

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 -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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP6V1B2	ENST00000521442.1	n.101-903T>G		intron_variant	Intron 1 of 3	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;