rs1040501

Variant names:

• chr1-169119076-A-G
• rs1040501
• NM_001677.4:c.227-5808A>G

Variant summary

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

The NM_001677.4(ATP1B1):​c.227-5808A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0712 in 152,284 control chromosomes in the GnomAD database, including 1,294 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 0.071 (1294 hom., cov: 33)
• Consequence: ATP1B1 NM_001677.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.94
• Publications: 1 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=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001677.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP1B1	NM_001677.4	MANE Select	c.227-5808A>G		intron	N/A	NP_001668.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP1B1	ENST00000367815.9	TSL:1 MANE Select	c.227-5808A>G		intron	N/A	ENSP00000356789.3
	ATP1B1	ENST00000367816.5	TSL:5	c.227-5808A>G		intron	N/A	ENSP00000356790.1
	ATP1B1	ENST00000689522.1		c.227-5808A>G		intron	N/A	ENSP00000509039.1

Frequencies

GnomAD3 genomes AF: 0.0710 AC: 10801 AN: 152166 Hom.: 1290 Cov.: 33

Gnomad AFR AF: 0.0870

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0836

Gnomad ASJ AF: 0.0393

Gnomad EAS AF: 0.599

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.0661

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0162

Gnomad OTH AF: 0.0684

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

GnomAD4 genome AF: 0.0712 AC: 10837 AN: 152284 Hom.: 1294 Cov.: 33 AF XY: 0.0782 AC XY: 5824 AN XY: 74458

African (AFR) AF: 0.0875 AC: 3635 AN: 41564

American (AMR) AF: 0.0840 AC: 1285 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0393 AC: 136 AN: 3464

East Asian (EAS) AF: 0.599 AC: 3096 AN: 5172

South Asian (SAS) AF: 0.147 AC: 707 AN: 4824

European-Finnish (FIN) AF: 0.0661 AC: 701 AN: 10612

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0162 AC: 1103 AN: 68034

Other (OTH) AF: 0.0743 AC: 157 AN: 2114

Alfa AF: 0.0330 Hom.: 289

Bravo AF: 0.0763

Asia WGS AF: 0.353 AC: 1225 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0030
DANN	Benign	0.34
PhyloP100		-1.9
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: rs1040501; hg19: chr1-169088314;