chr17-7656144-G-A

Variant names:

• chr17-7656144-G-A
• rs1641512
• NM_001678.5:c.*249G>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.*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
• Publications: 14 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.764 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001678.5. 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
	ATP1B2	NM_001678.5	MANE Select	c.*249G>A		3_prime_UTR	Exon 7 of 7	NP_001669.3
	ATP1B2	NM_001303263.2		c.*249G>A		3_prime_UTR	Exon 6 of 6	NP_001290192.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP1B2	ENST00000250111.9	TSL:1 MANE Select	c.*249G>A		3_prime_UTR	Exon 7 of 7	ENSP00000250111.4
	ATP1B2	ENST00000577113.1	TSL:3	c.*249G>A		downstream_gene	N/A	ENSP00000460499.1

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

African (AFR) AF: 0.705 AC: 8036 AN: 11404

American (AMR) AF: 0.775 AC: 13032 AN: 16816

Ashkenazi Jewish (ASJ) AF: 0.777 AC: 9506 AN: 12238

East Asian (EAS) AF: 0.634 AC: 16949 AN: 26718

South Asian (SAS) AF: 0.743 AC: 30902 AN: 41580

European-Finnish (FIN) AF: 0.738 AC: 18610 AN: 25226

Middle Eastern (MID) AF: 0.846 AC: 1493 AN: 1764

European-Non Finnish (NFE) AF: 0.775 AC: 186213 AN: 240268

Other (OTH) AF: 0.767 AC: 17590 AN: 22932

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

African (AFR) AF: 0.701 AC: 29011 AN: 41398

American (AMR) AF: 0.769 AC: 11734 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.776 AC: 2692 AN: 3470

East Asian (EAS) AF: 0.651 AC: 3359 AN: 5156

South Asian (SAS) AF: 0.734 AC: 3543 AN: 4824

European-Finnish (FIN) AF: 0.739 AC: 7806 AN: 10558

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

European-Non Finnish (NFE) AF: 0.769 AC: 52297 AN: 67974

Other (OTH) AF: 0.756 AC: 1595 AN: 2110

Alfa AF: 0.765 Hom.: 29013

Bravo AF: 0.742

Asia WGS AF: 0.671 AC: 2336 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	1.2
DANN	Benign	0.79
PhyloP100		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs1641512; hg19: chr17-7559462;