chr1-160161639-G-A

Variant names:

• chr1-160161639-G-A
• rs953104
• NM_144699.4:c.778+2113G>A

Variant summary

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

The NM_144699.4(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 NM_144699.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.292
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ATP1A4	NM_144699.4	c.778+2113G>A		intron_variant	Intron 6 of 21	ENST00000368081.9	NP_653300.2
ATP1A4	XM_011509582.2	c.601+2113G>A		intron_variant	Intron 5 of 20		XP_011507884.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP1A4	ENST00000368081.9	c.778+2113G>A		intron_variant	Intron 6 of 21	1	NM_144699.4	ENSP00000357060.4
ATP1A4	ENST00000477338.5	n.778+2113G>A		intron_variant	Intron 6 of 21	1		ENSP00000434272.1

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

African (AFR) AF: 0.761 AC: 31564 AN: 41484

American (AMR) AF: 0.884 AC: 13518 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.839 AC: 2908 AN: 3468

East Asian (EAS) AF: 0.996 AC: 5165 AN: 5184

South Asian (SAS) AF: 0.887 AC: 4271 AN: 4814

European-Finnish (FIN) AF: 0.826 AC: 8746 AN: 10588

Middle Eastern (MID) AF: 0.881 AC: 259 AN: 294

European-Non Finnish (NFE) AF: 0.848 AC: 57694 AN: 68002

Other (OTH) AF: 0.858 AC: 1811 AN: 2110

Alfa AF: 0.849 Hom.: 98924

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
PhyloP100		-0.29
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs953104; hg19: chr1-160131429;