1-169111599-C-T

Variant names:

• chr1-169111599-C-T
• rs1200138
• NM_001677.4:c.226+101C>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+101C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.754 in 1,467,256 control chromosomes in the GnomAD database, including 418,473 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 0.71 (39234 hom., cov: 32)
  • Exomes 𝑓: 0.76 (379239 hom.)
• Consequence: ATP1B1 NM_001677.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.73

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP1B1	NM_001677.4	c.226+101C>T		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.226+101C>T		intron_variant	Intron 2 of 5	1	NM_001677.4	ENSP00000356789.3

Frequencies

GnomAD3 genomes AF: 0.712 AC: 108177 AN: 151994 Hom.: 39216 Cov.: 32

Gnomad AFR AF: 0.561

Gnomad AMI AF: 0.752

Gnomad AMR AF: 0.753

Gnomad ASJ AF: 0.813

Gnomad EAS AF: 0.891

Gnomad SAS AF: 0.793

Gnomad FIN AF: 0.803

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.753

Gnomad OTH AF: 0.745

GnomAD4 exome AF: 0.758 AC: 997475 AN: 1315144 Hom.: 379239 AF XY: 0.760 AC XY: 492670 AN XY: 647900

Gnomad4 AFR exome AF: 0.562

Gnomad4 AMR exome AF: 0.782

Gnomad4 ASJ exome AF: 0.811

Gnomad4 EAS exome AF: 0.902

Gnomad4 SAS exome AF: 0.795

Gnomad4 FIN exome AF: 0.796

Gnomad4 NFE exome AF: 0.752

Gnomad4 OTH exome AF: 0.760

GnomAD4 genome AF: 0.712 AC: 108234 AN: 152112 Hom.: 39234 Cov.: 32 AF XY: 0.717 AC XY: 53326 AN XY: 74370

Gnomad4 AFR AF: 0.561

Gnomad4 AMR AF: 0.753

Gnomad4 ASJ AF: 0.813

Gnomad4 EAS AF: 0.891

Gnomad4 SAS AF: 0.792

Gnomad4 FIN AF: 0.803

Gnomad4 NFE AF: 0.753

Gnomad4 OTH AF: 0.746

Alfa AF: 0.754 Hom.: 56999

Bravo AF: 0.702

Asia WGS AF: 0.822 AC: 2859 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.12
DANN	Benign	0.73

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: rs1200138; hg19: chr1-169080837;