rs1642763

chr17-7654101-A-Gchr17-7654101-A-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001678.5(ATP1B2):c.396A>G(p.Gly132=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.769 in 1,613,966 control chromosomes in the GnomAD database, including 478,665 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 0.80 (49011 hom., cov: 31)
  • Exomes 𝑓: 0.77 (429654 hom.)
• Consequence: ATP1B2 NM_001678.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.339

Genes affected

ATP1B2 (HGNC:805): (ATPase Na+/K+ transporting subunit beta 2) 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 2 subunit. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2014]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP7: Synonymous conserved (PhyloP=-0.339 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.877 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP1B2	NM_001678.5	c.396A>G	p.Gly132=	synonymous_variant	4/7	ENST00000250111.9
ATP1B2	NM_001303263.2	c.150A>G	p.Gly50=	synonymous_variant	3/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP1B2	ENST00000250111.9	c.396A>G	p.Gly132=	synonymous_variant	4/7	1	NM_001678.5	P1
ATP1B2	ENST00000577026.5	c.150A>G	p.Gly50=	synonymous_variant	3/6	4
ATP1B2	ENST00000577113.1			upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.800 AC: 121620 AN: 152002 Hom.: 48964 Cov.: 31

Gnomad AFR AF: 0.884

Gnomad AMI AF: 0.751

Gnomad AMR AF: 0.793

Gnomad ASJ AF: 0.774

Gnomad EAS AF: 0.659

Gnomad SAS AF: 0.754

Gnomad FIN AF: 0.762

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.772

Gnomad OTH AF: 0.810

GnomAD3 exomes AF: 0.768 AC: 193043 AN: 251452 Hom.: 74485 AF XY: 0.768 AC XY: 104367 AN XY: 135910

Gnomad AFR exome AF: 0.887

Gnomad AMR exome AF: 0.771

Gnomad ASJ exome AF: 0.775

Gnomad EAS exome AF: 0.656

Gnomad SAS exome AF: 0.756

Gnomad FIN exome AF: 0.750

Gnomad NFE exome AF: 0.773

Gnomad OTH exome AF: 0.771

GnomAD4 exome AF: 0.766 AC: 1119532 AN: 1461846 Hom.: 429654 Cov.: 84 AF XY: 0.766 AC XY: 557352 AN XY: 727230

Gnomad4 AFR exome AF: 0.886

Gnomad4 AMR exome AF: 0.776

Gnomad4 ASJ exome AF: 0.776

Gnomad4 EAS exome AF: 0.632

Gnomad4 SAS exome AF: 0.760

Gnomad4 FIN exome AF: 0.749

Gnomad4 NFE exome AF: 0.766

Gnomad4 OTH exome AF: 0.778

GnomAD4 genome AF: 0.800 AC: 121722 AN: 152120 Hom.: 49011 Cov.: 31 AF XY: 0.798 AC XY: 59369 AN XY: 74354

Gnomad4 AFR AF: 0.884

Gnomad4 AMR AF: 0.793

Gnomad4 ASJ AF: 0.774

Gnomad4 EAS AF: 0.658

Gnomad4 SAS AF: 0.755

Gnomad4 FIN AF: 0.762

Gnomad4 NFE AF: 0.772

Gnomad4 OTH AF: 0.806

Alfa AF: 0.778 Hom.: 107833

Bravo AF: 0.803

Asia WGS AF: 0.693 AC: 2412 AN: 3478

EpiCase AF: 0.785

EpiControl AF: 0.786

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
Cadd	Benign	8.0
Dann	Benign	0.68

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: rs1642763; hg19: chr17-7557419; COSMIC: COSV51514774; COSMIC: COSV51514774;