17-7656359-G-A

Variant names:

• chr17-7656359-G-A
• rs1641511
• NM_001678.5:c.*464G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001678.5(ATP1B2):​c.*464G>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 0.72 in 171,492 control chromosomes in the GnomAD database, including 44,981 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 0.72 (39221 hom., cov: 28)
  • Exomes 𝑓: 0.75 (5760 hom.)
• Consequence: ATP1B2 NM_001678.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.852
• Publications: 23 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP1B2	NM_001678.5	c.*464G>A		3_prime_UTR_variant	Exon 7 of 7	ENST00000250111.9	NP_001669.3
ATP1B2	NM_001303263.2	c.*464G>A		3_prime_UTR_variant	Exon 6 of 6		NP_001290192.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP1B2	ENST00000250111.9	c.*464G>A		3_prime_UTR_variant	Exon 7 of 7	1	NM_001678.5	ENSP00000250111.4

Frequencies

GnomAD3 genomes AF: 0.716 AC: 108314 AN: 151260 Hom.: 39190 Cov.: 28

Gnomad AFR AF: 0.606

Gnomad AMI AF: 0.749

Gnomad AMR AF: 0.756

Gnomad ASJ AF: 0.776

Gnomad EAS AF: 0.646

Gnomad SAS AF: 0.725

Gnomad FIN AF: 0.741

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.769

Gnomad OTH AF: 0.744

GnomAD4 exome AF: 0.748 AC: 15039 AN: 20114 Hom.: 5760 Cov.: 0 AF XY: 0.746 AC XY: 7884 AN XY: 10572

African (AFR) AF: 0.578 AC: 342 AN: 592

American (AMR) AF: 0.772 AC: 2167 AN: 2808

Ashkenazi Jewish (ASJ) AF: 0.787 AC: 274 AN: 348

East Asian (EAS) AF: 0.634 AC: 786 AN: 1240

South Asian (SAS) AF: 0.715 AC: 1697 AN: 2372

European-Finnish (FIN) AF: 0.748 AC: 335 AN: 448

Middle Eastern (MID) AF: 0.868 AC: 33 AN: 38

European-Non Finnish (NFE) AF: 0.768 AC: 8685 AN: 11314

Other (OTH) AF: 0.755 AC: 720 AN: 954

GnomAD4 genome AF: 0.716 AC: 108396 AN: 151378 Hom.: 39221 Cov.: 28 AF XY: 0.717 AC XY: 52975 AN XY: 73928

African (AFR) AF: 0.607 AC: 24988 AN: 41160

American (AMR) AF: 0.756 AC: 11460 AN: 15162

Ashkenazi Jewish (ASJ) AF: 0.776 AC: 2688 AN: 3464

East Asian (EAS) AF: 0.645 AC: 3304 AN: 5120

South Asian (SAS) AF: 0.726 AC: 3481 AN: 4792

European-Finnish (FIN) AF: 0.741 AC: 7758 AN: 10474

Middle Eastern (MID) AF: 0.915 AC: 269 AN: 294

European-Non Finnish (NFE) AF: 0.769 AC: 52213 AN: 67902

Other (OTH) AF: 0.740 AC: 1552 AN: 2098

Alfa AF: 0.753 Hom.: 167826

Bravo AF: 0.708

Asia WGS AF: 0.656 AC: 2282 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	0.56
DANN	Benign	0.71
PhyloP100		-0.85
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: rs1641511; hg19: chr17-7559677;