chr1-169111599-C-T

Variant names:

• chr1-169111599-C-T
• rs1200138
• NM_001677.4:c.226+101C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.869 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.226+101C>T		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.226+101C>T		intron	N/A	ENSP00000356789.3
	ATP1B1	ENST00000367816.5	TSL:5	c.226+101C>T		intron	N/A	ENSP00000356790.1
	ATP1B1	ENST00000689522.1		c.226+101C>T		intron	N/A	ENSP00000509039.1

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

African (AFR) AF: 0.562 AC: 16402 AN: 29182

American (AMR) AF: 0.782 AC: 23780 AN: 30404

Ashkenazi Jewish (ASJ) AF: 0.811 AC: 16888 AN: 20830

East Asian (EAS) AF: 0.902 AC: 34665 AN: 38434

South Asian (SAS) AF: 0.795 AC: 54737 AN: 68814

European-Finnish (FIN) AF: 0.796 AC: 34440 AN: 43256

Middle Eastern (MID) AF: 0.847 AC: 4460 AN: 5266

European-Non Finnish (NFE) AF: 0.752 AC: 770529 AN: 1024224

Other (OTH) AF: 0.760 AC: 41574 AN: 54734

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

African (AFR) AF: 0.561 AC: 23226 AN: 41422

American (AMR) AF: 0.753 AC: 11532 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.813 AC: 2821 AN: 3472

East Asian (EAS) AF: 0.891 AC: 4615 AN: 5180

South Asian (SAS) AF: 0.792 AC: 3823 AN: 4826

European-Finnish (FIN) AF: 0.803 AC: 8505 AN: 10592

Middle Eastern (MID) AF: 0.806 AC: 237 AN: 294

European-Non Finnish (NFE) AF: 0.753 AC: 51211 AN: 67992

Other (OTH) AF: 0.746 AC: 1578 AN: 2116

Alfa AF: 0.748 Hom.: 70911

Bravo AF: 0.702

Asia WGS AF: 0.822 AC: 2859 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.12
DANN	Benign	0.73
PhyloP100		-1.7
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: rs1200138; hg19: chr1-169080837;