rs1106634

Variant names:

• chr8-20208538-G-A
• rs1106634
• NM_001693.4:c.193-895G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-20208538-G-A
• chr8-20208538-G-C
• chr8-20208538-G-T

Variant summary

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

The NM_001693.4(ATP6V1B2):​c.193-895G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 152,044 control chromosomes in the GnomAD database, including 2,569 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 0.18 (2569 hom., cov: 32)
• Consequence: ATP6V1B2 NM_001693.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.222
• Publications: 24 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP6V1B2	NM_001693.4	c.193-895G>A		intron_variant	Intron 2 of 13	ENST00000276390.7	NP_001684.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP6V1B2	ENST00000276390.7	c.193-895G>A		intron_variant	Intron 2 of 13	1	NM_001693.4	ENSP00000276390.2

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26917 AN: 151926 Hom.: 2568 Cov.: 32

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.0965

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.0654

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.163

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

GnomAD4 genome AF: 0.177 AC: 26935 AN: 152044 Hom.: 2569 Cov.: 32 AF XY: 0.176 AC XY: 13046 AN XY: 74326

African (AFR) AF: 0.234 AC: 9712 AN: 41460

American (AMR) AF: 0.235 AC: 3597 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0654 AC: 227 AN: 3470

East Asian (EAS) AF: 0.151 AC: 784 AN: 5180

South Asian (SAS) AF: 0.179 AC: 862 AN: 4824

European-Finnish (FIN) AF: 0.122 AC: 1291 AN: 10558

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.147 AC: 10005 AN: 67960

Other (OTH) AF: 0.164 AC: 346 AN: 2108

Alfa AF: 0.155 Hom.: 3845

Bravo AF: 0.186

Asia WGS AF: 0.163 AC: 568 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.57
DANN	Benign	0.73
PhyloP100		-0.22
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1106634; hg19: chr8-20066049;