rs2982468

Variant names:

• chr1-169121733-T-A
• rs2982468
• NM_001677.4:c.227-3151T>A

Variant summary

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

The NM_001677.4(ATP1B1):​c.227-3151T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0753 in 152,286 control chromosomes in the GnomAD database, including 628 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 0.075 (628 hom., cov: 32)
• Consequence: ATP1B1 NM_001677.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0600
• Publications: 5 publications found

Genes affected

ATP1B1 (HGNC:804): (ATPase Na+/K+ transporting subunit beta 1) The protein encoded by this gene belongs to the family of Na+/K+ and H+/K+ ATPases beta chain proteins, 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 beta subunit regulates, through assembly of alpha/beta heterodimers, the number of sodium pumps transported to the plasma membrane. The glycoprotein subunit of Na+/K+ -ATPase is encoded by multiple genes. This gene encodes a beta 1 subunit. Alternatively spliced transcript variants encoding different isoforms have been described, but their biological validity is not known. [provided by RefSeq, Mar 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP1B1	NM_001677.4	c.227-3151T>A		intron_variant	Intron 2 of 5	ENST00000367815.9	NP_001668.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP1B1	ENST00000367815.9	c.227-3151T>A		intron_variant	Intron 2 of 5	1	NM_001677.4	ENSP00000356789.3

Frequencies

GnomAD3 genomes AF: 0.0751 AC: 11428 AN: 152166 Hom.: 620 Cov.: 32

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.0330

Gnomad AMR AF: 0.0570

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.0886

Gnomad FIN AF: 0.00706

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0471

Gnomad OTH AF: 0.0750

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

GnomAD4 genome AF: 0.0753 AC: 11460 AN: 152286 Hom.: 628 Cov.: 32 AF XY: 0.0749 AC XY: 5576 AN XY: 74472

African (AFR) AF: 0.133 AC: 5534 AN: 41554

American (AMR) AF: 0.0569 AC: 870 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 438 AN: 3470

East Asian (EAS) AF: 0.132 AC: 686 AN: 5186

South Asian (SAS) AF: 0.0888 AC: 428 AN: 4820

European-Finnish (FIN) AF: 0.00706 AC: 75 AN: 10618

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0472 AC: 3207 AN: 68016

Other (OTH) AF: 0.0761 AC: 161 AN: 2116

Alfa AF: 0.0581 Hom.: 37

Bravo AF: 0.0804

Asia WGS AF: 0.107 AC: 370 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.3
DANN	Benign	0.78
PhyloP100		0.060
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: rs2982468; hg19: chr1-169090971;