1-43976849-A-T

Position:

• chr1-43976849-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004047.5(ATP6V0B):​c.400+25A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: ATP6V0B NM_004047.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.125

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]

ATP6V0B (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP6V0B	NM_004047.5	c.400+25A>T		intron_variant		ENST00000472174.7	NP_004038.1
ATP6V0B	NM_001294333.2	c.400+25A>T		intron_variant			NP_001281262.1
ATP6V0B	NM_001039457.3	c.259+25A>T		intron_variant			NP_001034546.1
ATP6V0B	XM_047422650.1	c.259+25A>T		intron_variant			XP_047278606.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP6V0B	ENST00000472174.7	c.400+25A>T		intron_variant		1	NM_004047.5	ENSP00000431605.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 54

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.4
DANN	Benign	0.69
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Publications

LitVar

Other links and lift over

dbSNP: rs12410334; hg19: chr1-44442521;