rs3766031

Positions:

• chr1-169115881-C-T

Variant summary

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

The NM_001677.4(ATP1B1):​c.226+4383C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 152,274 control chromosomes in the GnomAD database, including 1,076 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 0.11 (1076 hom., cov: 32)
• Consequence: ATP1B1 NM_001677.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.427

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP1B1	NM_001677.4	c.226+4383C>T		intron_variant		ENST00000367815.9	NP_001668.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP1B1	ENST00000367815.9	c.226+4383C>T		intron_variant		1	NM_001677.4	ENSP00000356789	P1

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16651 AN: 152156 Hom.: 1076 Cov.: 32

Gnomad AFR AF: 0.0604

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.123

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

GnomAD4 genome AF: 0.109 AC: 16654 AN: 152274 Hom.: 1076 Cov.: 32 AF XY: 0.109 AC XY: 8115 AN XY: 74458

Gnomad4 AFR AF: 0.0604

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.215

Gnomad4 EAS AF: 0.144

Gnomad4 SAS AF: 0.103

Gnomad4 FIN AF: 0.105

Gnomad4 NFE AF: 0.128

Gnomad4 OTH AF: 0.122

Alfa AF: 0.125 Hom.: 1660

Bravo AF: 0.108

Asia WGS AF: 0.108 AC: 374 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.5
DANN	Benign	0.41

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: rs3766031; hg19: chr1-169085119;