chr8-20224379-T-G

Variant names:

• chr8-20224379-T-G
• rs1390943
• ENST00000718265.1:n.*3977T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000718265.1(ATP6V1B2):​n.*3977T>G variant causes a non coding transcript exon 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 ENST00000718265.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.167
• Publications: 7 publications found

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]

ATP6V1B2 Gene-Disease associations (from GenCC):

• autosomal dominant deafness - onychodystrophy syndrome

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
• developmental and epileptic encephalopathy 93

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• neurodevelopmental disorder

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics
• Zimmermann-Laband syndrome 2

  Inheritance: AD Classification: STRONG Submitted by: G2P
• DOORS syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Zimmermann-Laband syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000309971 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000718265.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP6V1B2	ENST00000718265.1		n.*3977T>G		non_coding_transcript_exon	Exon 14 of 15	ENSP00000520705.1
	ATP6V1B2	ENST00000718266.1		c.*3977T>G		3_prime_UTR	Exon 14 of 14	ENSP00000520706.1
	ATP6V1B2	ENST00000718265.1		n.*3977T>G		3_prime_UTR	Exon 14 of 15	ENSP00000520705.1

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

African (AFR) AF: 0.656 AC: 26330 AN: 40150

American (AMR) AF: 0.430 AC: 6533 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.364 AC: 1264 AN: 3468

East Asian (EAS) AF: 0.240 AC: 1246 AN: 5184

South Asian (SAS) AF: 0.281 AC: 1354 AN: 4818

European-Finnish (FIN) AF: 0.222 AC: 2351 AN: 10594

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.336 AC: 22852 AN: 67958

Other (OTH) AF: 0.421 AC: 884 AN: 2102

Alfa AF: 0.357 Hom.: 42153

Bravo AF: 0.444

Asia WGS AF: 0.277 AC: 965 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.23
DANN	Benign	0.47
PhyloP100		-0.17

Splicing

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

Other links and lift over

dbSNP: rs1390943; hg19: chr8-20081890;