rs748214

Positions:

• chr19-35557889-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000704.3(ATP4A):​c.1501-42C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 1,060,460 control chromosomes in the GnomAD database, including 57,848 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 0.28 (6608 hom., cov: 23)
  • Exomes 𝑓: 0.28 (51240 hom.)
• Consequence: ATP4A NM_000704.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.363

Genes affected

ATP4A (HGNC:819): (ATPase H+/K+ transporting subunit alpha) The protein encoded by this gene belongs to a family of P-type cation-transporting ATPases. The gastric H+, K+-ATPase is a heterodimer consisting of a high molecular weight catalytic alpha subunit and a smaller but heavily glycosylated beta subunit. This enzyme is a proton pump that catalyzes the hydrolysis of ATP coupled with the exchange of H(+) and K(+) ions across the plasma membrane. It is also responsible for gastric acid secretion. This gene encodes a catalytic alpha subunit of the gastric H+, K+-ATPase. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP4A	NM_000704.3	c.1501-42C>T		intron_variant		ENST00000262623.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP4A	ENST00000262623.4	c.1501-42C>T		intron_variant		1	NM_000704.3	P1
	ENST00000702449.1			upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.283 AC: 41499 AN: 146524 Hom.: 6610 Cov.: 23

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.236

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.406

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.313

GnomAD3 exomes AF: 0.233 AC: 8600 AN: 36950 Hom.: 1663 AF XY: 0.247 AC XY: 4784 AN XY: 19386

Gnomad AFR exome AF: 0.0948

Gnomad AMR exome AF: 0.124

Gnomad ASJ exome AF: 0.250

Gnomad EAS exome AF: 0.183

Gnomad SAS exome AF: 0.315

Gnomad FIN exome AF: 0.361

Gnomad NFE exome AF: 0.307

Gnomad OTH exome AF: 0.223

GnomAD4 exome AF: 0.278 AC: 254266 AN: 913830 Hom.: 51240 Cov.: 13 AF XY: 0.284 AC XY: 127610 AN XY: 449648

Gnomad4 AFR exome AF: 0.110

Gnomad4 AMR exome AF: 0.160

Gnomad4 ASJ exome AF: 0.328

Gnomad4 EAS exome AF: 0.166

Gnomad4 SAS exome AF: 0.328

Gnomad4 FIN exome AF: 0.364

Gnomad4 NFE exome AF: 0.283

Gnomad4 OTH exome AF: 0.282

GnomAD4 genome AF: 0.283 AC: 41498 AN: 146630 Hom.: 6608 Cov.: 23 AF XY: 0.281 AC XY: 20042 AN XY: 71346

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.233

Gnomad4 ASJ AF: 0.366

Gnomad4 EAS AF: 0.236

Gnomad4 SAS AF: 0.336

Gnomad4 FIN AF: 0.347

Gnomad4 NFE AF: 0.357

Gnomad4 OTH AF: 0.312

Alfa AF: 0.301 Hom.: 769

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.7
DANN	Benign	0.94

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs748214; hg19: chr19-36048791;