rs1641512

chr17-7656144-G-Achr17-7656144-G-Cchr17-7656144-G-T

Variant summary

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

The NM_001678.5(ATP1B2):c.*249G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.754 in 550,894 control chromosomes in the GnomAD database, including 157,169 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 0.74 (42165 hom., cov: 30)
  • Exomes 𝑓: 0.76 (115004 hom.)
• Consequence: ATP1B2 NM_001678.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16

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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.764 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP1B2	NM_001678.5	c.*249G>A		3_prime_UTR_variant	7/7	ENST00000250111.9
ATP1B2	NM_001303263.2	c.*249G>A		3_prime_UTR_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP1B2	ENST00000250111.9	c.*249G>A		3_prime_UTR_variant	7/7	1	NM_001678.5	P1

Frequencies

GnomAD3 genomes AF: 0.744 AC: 112902 AN: 151830 Hom.: 42132 Cov.: 30

Gnomad AFR AF: 0.700

Gnomad AMI AF: 0.749

Gnomad AMR AF: 0.770

Gnomad ASJ AF: 0.776

Gnomad EAS AF: 0.652

Gnomad SAS AF: 0.733

Gnomad FIN AF: 0.739

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.769

Gnomad OTH AF: 0.761

GnomAD4 exome AF: 0.758 AC: 302331 AN: 398946 Hom.: 115004 Cov.: 4 AF XY: 0.758 AC XY: 158426 AN XY: 209048

Gnomad4 AFR exome AF: 0.705

Gnomad4 AMR exome AF: 0.775

Gnomad4 ASJ exome AF: 0.777

Gnomad4 EAS exome AF: 0.634

Gnomad4 SAS exome AF: 0.743

Gnomad4 FIN exome AF: 0.738

Gnomad4 NFE exome AF: 0.775

Gnomad4 OTH exome AF: 0.767

GnomAD4 genome AF: 0.744 AC: 112989 AN: 151948 Hom.: 42165 Cov.: 30 AF XY: 0.744 AC XY: 55217 AN XY: 74248

Gnomad4 AFR AF: 0.701

Gnomad4 AMR AF: 0.769

Gnomad4 ASJ AF: 0.776

Gnomad4 EAS AF: 0.651

Gnomad4 SAS AF: 0.734

Gnomad4 FIN AF: 0.739

Gnomad4 NFE AF: 0.769

Gnomad4 OTH AF: 0.756

Alfa AF: 0.766 Hom.: 14057

Bravo AF: 0.742

Asia WGS AF: 0.671 AC: 2336 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	1.2
Dann	Benign	0.79
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1641512; hg19: chr17-7559462;