chr1-43975861-A-G

Variant names:

• chr1-43975861-A-G
• rs2286243
• NM_004047.5:c.116+13A>G

Variant summary

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

The NM_001294333.2(ATP6V0B):​c.116+13A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0593 in 1,587,268 control chromosomes in the GnomAD database, including 3,315 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 0.070 (430 hom., cov: 33)
  • Exomes 𝑓: 0.058 (2885 hom.)
• Consequence: ATP6V0B NM_001294333.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.291
• Publications: 15 publications found

Genes affected

ATP6V0B (HGNC:861): (ATPase H+ transporting V0 subunit b) This gene encodes a portion of the V0 domain of vacuolar ATPase (V-ATPase), a multisubunit enzyme that mediates acidification of eukaryotic intracellular organelles. Activity of this enzyme is necessary for such varied processes as protein sorting, zymogen activation, receptor-mediated endocytosis, and synaptic vesicle proton gradient generation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001294333.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP6V0B	NM_004047.5	MANE Select	c.116+13A>G		intron	N/A	NP_004038.1
	ATP6V0B	NM_001294333.2		c.116+13A>G		intron	N/A	NP_001281262.1
	ATP6V0B	NM_001039457.3		c.-25-229A>G		intron	N/A	NP_001034546.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP6V0B	ENST00000472174.7	TSL:1 MANE Select	c.116+13A>G		intron	N/A	ENSP00000431605.1
	ATP6V0B	ENST00000468183.5	TSL:1	n.878+13A>G		intron	N/A
	ATP6V0B	ENST00000532642.5	TSL:2	c.116+13A>G		intron	N/A	ENSP00000434729.1

Frequencies

GnomAD3 genomes AF: 0.0699 AC: 10624 AN: 152084 Hom.: 429 Cov.: 33

Gnomad AFR AF: 0.0964

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0714

Gnomad ASJ AF: 0.0485

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.0779

Gnomad FIN AF: 0.0290

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0533

Gnomad OTH AF: 0.0775

GnomAD2 exomes AF: 0.0679 AC: 15722 AN: 231558 AF XY: 0.0675

Gnomad AFR exome AF: 0.0929

Gnomad AMR exome AF: 0.0747

Gnomad ASJ exome AF: 0.0408

Gnomad EAS exome AF: 0.170

Gnomad FIN exome AF: 0.0301

Gnomad NFE exome AF: 0.0521

Gnomad OTH exome AF: 0.0637

GnomAD4 exome AF: 0.0582 AC: 83489 AN: 1435066 Hom.: 2885 Cov.: 32 AF XY: 0.0583 AC XY: 41452 AN XY: 711448

African (AFR) AF: 0.0956 AC: 3094 AN: 32374

American (AMR) AF: 0.0730 AC: 2998 AN: 41078

Ashkenazi Jewish (ASJ) AF: 0.0448 AC: 1104 AN: 24652

East Asian (EAS) AF: 0.163 AC: 6429 AN: 39322

South Asian (SAS) AF: 0.0752 AC: 6245 AN: 83002

European-Finnish (FIN) AF: 0.0297 AC: 1562 AN: 52668

Middle Eastern (MID) AF: 0.0502 AC: 282 AN: 5612

European-Non Finnish (NFE) AF: 0.0528 AC: 57910 AN: 1097212

Other (OTH) AF: 0.0653 AC: 3865 AN: 59146

GnomAD4 genome AF: 0.0699 AC: 10642 AN: 152202 Hom.: 430 Cov.: 33 AF XY: 0.0705 AC XY: 5249 AN XY: 74408

African (AFR) AF: 0.0964 AC: 4004 AN: 41530

American (AMR) AF: 0.0717 AC: 1096 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0485 AC: 168 AN: 3466

East Asian (EAS) AF: 0.166 AC: 860 AN: 5168

South Asian (SAS) AF: 0.0782 AC: 377 AN: 4822

European-Finnish (FIN) AF: 0.0290 AC: 307 AN: 10594

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0533 AC: 3622 AN: 68008

Other (OTH) AF: 0.0805 AC: 170 AN: 2112

Alfa AF: 0.0584 Hom.: 375

Bravo AF: 0.0732

Asia WGS AF: 0.126 AC: 438 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.1
DANN	Benign	0.83
PhyloP100		-0.29
PromoterAI		0.13	Neutral
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: rs2286243; hg19: chr1-44441533; COSMIC: COSV52542880; COSMIC: COSV52542880;