17-7654516-C-T

Position:

• chr17-7654516-C-T

Variant summary

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

The NM_001678.5(ATP1B2):​c.553-112C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 1,200,116 control chromosomes in the GnomAD database, including 152,513 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 0.45 (16587 hom., cov: 30)
  • Exomes 𝑓: 0.50 (135926 hom.)
• Consequence: ATP1B2 NM_001678.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.803

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP1B2	NM_001678.5	c.553-112C>T		intron_variant		ENST00000250111.9	NP_001669.3
ATP1B2	NM_001303263.2	c.307-112C>T		intron_variant			NP_001290192.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP1B2	ENST00000250111.9	c.553-112C>T		intron_variant		1	NM_001678.5	ENSP00000250111	P1
ATP1B2	ENST00000577026.5	c.307-112C>T		intron_variant		4		ENSP00000459145
ATP1B2	ENST00000577113.1	c.150-112C>T		intron_variant		3		ENSP00000460499

Frequencies

GnomAD3 genomes AF: 0.454 AC: 68929 AN: 151738 Hom.: 16594 Cov.: 30

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.594

Gnomad AMR AF: 0.480

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.575

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.528

Gnomad OTH AF: 0.483

GnomAD4 exome AF: 0.505 AC: 528897 AN: 1048258 Hom.: 135926 AF XY: 0.501 AC XY: 268257 AN XY: 535348

Gnomad4 AFR exome AF: 0.283

Gnomad4 AMR exome AF: 0.486

Gnomad4 ASJ exome AF: 0.507

Gnomad4 EAS exome AF: 0.537

Gnomad4 SAS exome AF: 0.372

Gnomad4 FIN exome AF: 0.531

Gnomad4 NFE exome AF: 0.523

Gnomad4 OTH exome AF: 0.502

GnomAD4 genome AF: 0.454 AC: 68920 AN: 151858 Hom.: 16587 Cov.: 30 AF XY: 0.455 AC XY: 33758 AN XY: 74184

Gnomad4 AFR AF: 0.285

Gnomad4 AMR AF: 0.479

Gnomad4 ASJ AF: 0.505

Gnomad4 EAS AF: 0.574

Gnomad4 SAS AF: 0.384

Gnomad4 FIN AF: 0.538

Gnomad4 NFE AF: 0.528

Gnomad4 OTH AF: 0.479

Alfa AF: 0.345 Hom.: 943

Bravo AF: 0.444

Asia WGS AF: 0.447 AC: 1554 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.62
DANN	Benign	0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1642764; hg19: chr17-7557834; COSMIC: COSV51515227;