22-17596752-T-C

Variant names:

• chr22-17596752-T-C
• rs1296826
• NM_001696.4:c.530+1442A>G

Variant summary

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

The NM_001696.4(ATP6V1E1):​c.530+1442A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 152,048 control chromosomes in the GnomAD database, including 2,957 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 0.15 (2957 hom., cov: 32)
• Consequence: ATP6V1E1 NM_001696.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.368
• Publications: 7 publications found

Genes affected

ATP6V1E1 (HGNC:857): (ATPase H+ transporting V1 subunit E1) 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. This gene encodes alternate transcriptional splice variants, encoding different V1 domain E subunit isoforms. Pseudogenes for this gene have been found in the genome. [provided by RefSeq, Jul 2008]

ATP6V1E1 Gene-Disease associations (from GenCC):

• autosomal recessive cutis laxa type 2C

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P
• autosomal recessive cutis laxa type 2, classic type

  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 (AFR) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP6V1E1	NM_001696.4	c.530+1442A>G		intron_variant	Intron 7 of 8	ENST00000253413.10	NP_001687.1
ATP6V1E1	NM_001039366.1	c.464+1442A>G		intron_variant	Intron 6 of 7		NP_001034455.1
ATP6V1E1	NM_001039367.1	c.440+1442A>G		intron_variant	Intron 6 of 7		NP_001034456.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP6V1E1	ENST00000253413.10	c.530+1442A>G		intron_variant	Intron 7 of 8	1	NM_001696.4	ENSP00000253413.5
ATP6V1E1	ENST00000399798.6	c.464+1442A>G		intron_variant	Intron 6 of 7	2		ENSP00000382696.2
ATP6V1E1	ENST00000413576.1	c.533+1442A>G		intron_variant	Intron 8 of 8	3		ENSP00000398932.1
ATP6V1E1	ENST00000399796.6	c.440+1442A>G		intron_variant	Intron 6 of 7	2		ENSP00000382694.2

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22055 AN: 151930 Hom.: 2951 Cov.: 32

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.0880

Gnomad FIN AF: 0.0132

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0632

Gnomad OTH AF: 0.126

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

GnomAD4 genome AF: 0.145 AC: 22087 AN: 152048 Hom.: 2957 Cov.: 32 AF XY: 0.142 AC XY: 10536 AN XY: 74348

African (AFR) AF: 0.345 AC: 14243 AN: 41340

American (AMR) AF: 0.103 AC: 1568 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 393 AN: 3472

East Asian (EAS) AF: 0.136 AC: 707 AN: 5182

South Asian (SAS) AF: 0.0882 AC: 426 AN: 4828

European-Finnish (FIN) AF: 0.0132 AC: 140 AN: 10618

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0632 AC: 4296 AN: 68018

Other (OTH) AF: 0.125 AC: 263 AN: 2108

Alfa AF: 0.0986 Hom.: 1076

Bravo AF: 0.162

Asia WGS AF: 0.124 AC: 435 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	1.0
DANN	Benign	0.72
PhyloP100		-0.37
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1296826; hg19: chr22-18079518;