1-43975097-G-C

Variant names:

• chr1-43975097-G-C
• rs2286241
• NM_004047.5:c.57G>C
• ATP6V0B p.Ala19Ala

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_004047.5(ATP6V0B):​c.57G>C​(p.Ala19Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0563 in 1,407,126 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 0.058 (283 hom., cov: 33)
  • Exomes 𝑓: 0.056 (2286 hom.)
• Consequence: ATP6V0B NM_004047.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.515
• 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]

LOC124904167 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP7: Synonymous conserved (PhyloP=0.515 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004047.5. 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.57G>C	p.Ala19Ala	synonymous	Exon 1 of 8	NP_004038.1	Q99437-1
	ATP6V0B	NM_001294333.2		c.57G>C	p.Ala19Ala	synonymous	Exon 1 of 7	NP_001281262.1	E9PNL3
	ATP6V0B	NM_001039457.3		c.-36G>C		5_prime_UTR	Exon 1 of 7	NP_001034546.1	Q99437-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP6V0B	ENST00000472174.7	TSL:1 MANE Select	c.57G>C	p.Ala19Ala	synonymous	Exon 1 of 8	ENSP00000431605.1	Q99437-1
	ATP6V0B	ENST00000468183.5	TSL:1	n.127G>C		non_coding_transcript_exon	Exon 1 of 6
	ATP6V0B	ENST00000532642.5	TSL:2	c.57G>C	p.Ala19Ala	synonymous	Exon 1 of 7	ENSP00000434729.1	E9PNL3

Frequencies

GnomAD3 genomes AF: 0.0584 AC: 8886 AN: 152180 Hom.: 282 Cov.: 33

Gnomad AFR AF: 0.0560

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0680

Gnomad ASJ AF: 0.0479

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.0778

Gnomad FIN AF: 0.0290

Gnomad MID AF: 0.0573

Gnomad NFE AF: 0.0531

Gnomad OTH AF: 0.0707

GnomAD2 exomes AF: 0.0580 AC: 1524 AN: 26288 AF XY: 0.0582

Gnomad AFR exome AF: 0.0646

Gnomad AMR exome AF: 0.0630

Gnomad ASJ exome AF: 0.0320

Gnomad EAS exome AF: 0.141

Gnomad FIN exome AF: 0.0251

Gnomad NFE exome AF: 0.0485

Gnomad OTH exome AF: 0.0533

GnomAD4 exome AF: 0.0561 AC: 70337 AN: 1254828 Hom.: 2286 Cov.: 31 AF XY: 0.0562 AC XY: 34288 AN XY: 610496

African (AFR) AF: 0.0526 AC: 1274 AN: 24206

American (AMR) AF: 0.0637 AC: 946 AN: 14852

Ashkenazi Jewish (ASJ) AF: 0.0469 AC: 831 AN: 17736

East Asian (EAS) AF: 0.162 AC: 4607 AN: 28480

South Asian (SAS) AF: 0.0733 AC: 4396 AN: 59946

European-Finnish (FIN) AF: 0.0290 AC: 1002 AN: 34606

Middle Eastern (MID) AF: 0.0494 AC: 243 AN: 4922

European-Non Finnish (NFE) AF: 0.0528 AC: 53790 AN: 1018350

Other (OTH) AF: 0.0628 AC: 3248 AN: 51730

GnomAD4 genome AF: 0.0584 AC: 8900 AN: 152298 Hom.: 283 Cov.: 33 AF XY: 0.0593 AC XY: 4419 AN XY: 74472

African (AFR) AF: 0.0561 AC: 2333 AN: 41576

American (AMR) AF: 0.0683 AC: 1045 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0479 AC: 166 AN: 3466

East Asian (EAS) AF: 0.167 AC: 865 AN: 5172

South Asian (SAS) AF: 0.0780 AC: 377 AN: 4832

European-Finnish (FIN) AF: 0.0290 AC: 308 AN: 10620

Middle Eastern (MID) AF: 0.0445 AC: 13 AN: 292

European-Non Finnish (NFE) AF: 0.0531 AC: 3612 AN: 68008

Other (OTH) AF: 0.0737 AC: 156 AN: 2116

Alfa AF: 0.0535 Hom.: 32

Bravo AF: 0.0605

Asia WGS AF: 0.123 AC: 428 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	14
DANN	Benign	0.89
PhyloP100		0.52
PromoterAI		-0.047	Neutral
Mutation Taster		=298/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2286241;

hg19: chr1-44440769;

COSMIC: COSV52542892;

COSMIC: COSV52542892;