rs953104

Positions:

• chr1-160161639-G-A
• chr1-160161639-G-C

Variant summary

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

The ENST00000368081.9(ATP1A4):​c.778+2113G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.833 in 152,146 control chromosomes in the GnomAD database, including 53,109 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 0.83 (53109 hom., cov: 31)
• Consequence: ATP1A4 ENST00000368081.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.292

Genes affected

ATP1A4 (HGNC:14073): (ATPase Na+/K+ transporting subunit alpha 4) The protein encoded by this gene belongs to the family of P-type cation transport ATPases, and to the subfamily of Na+/K+ -ATPases. Na+/K+ -ATPase is an integral membrane protein responsible for establishing and maintaining the electrochemical gradients of Na and K ions across the plasma membrane. These gradients are essential for osmoregulation, for sodium-coupled transport of a variety of organic and inorganic molecules, and for electrical excitability of nerve and muscle. This enzyme is composed of two subunits, a large catalytic subunit (alpha) and a smaller glycoprotein subunit (beta). The catalytic subunit of Na+/K+ -ATPase is encoded by multiple genes. This gene encodes an alpha 4 subunit. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP1A4	NM_144699.4	c.778+2113G>A		intron_variant		ENST00000368081.9	NP_653300.2
ATP1A4	XM_011509582.2	c.601+2113G>A		intron_variant			XP_011507884.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP1A4	ENST00000368081.9	c.778+2113G>A		intron_variant		1	NM_144699.4	ENSP00000357060	P1
ATP1A4	ENST00000477338.5	c.778+2113G>A		intron_variant, NMD_transcript_variant		1		ENSP00000434272

Frequencies

GnomAD3 genomes AF: 0.833 AC: 126714 AN: 152028 Hom.: 53074 Cov.: 31

Gnomad AFR AF: 0.761

Gnomad AMI AF: 0.950

Gnomad AMR AF: 0.884

Gnomad ASJ AF: 0.839

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.886

Gnomad FIN AF: 0.826

Gnomad MID AF: 0.880

Gnomad NFE AF: 0.848

Gnomad OTH AF: 0.858

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

GnomAD4 genome AF: 0.833 AC: 126802 AN: 152146 Hom.: 53109 Cov.: 31 AF XY: 0.835 AC XY: 62078 AN XY: 74384

Gnomad4 AFR AF: 0.761

Gnomad4 AMR AF: 0.884

Gnomad4 ASJ AF: 0.839

Gnomad4 EAS AF: 0.996

Gnomad4 SAS AF: 0.887

Gnomad4 FIN AF: 0.826

Gnomad4 NFE AF: 0.848

Gnomad4 OTH AF: 0.858

Alfa AF: 0.850 Hom.: 70321

Bravo AF: 0.837

Asia WGS AF: 0.935 AC: 3253 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.53
DANN	Benign	0.56

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: rs953104; hg19: chr1-160131429;