chr17-7654516-C-T

Variant names:

• chr17-7654516-C-T
• rs1642764
• NM_001678.5:c.553-112C>T

Variant summary

Our verdict is Benign. The variant received -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
• 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 (EAS) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP1B2	NM_001678.5	c.553-112C>T		intron_variant	Intron 4 of 6	ENST00000250111.9	NP_001669.3
ATP1B2	NM_001303263.2	c.307-112C>T		intron_variant	Intron 3 of 5		NP_001290192.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP1B2	ENST00000250111.9	c.553-112C>T		intron_variant	Intron 4 of 6	1	NM_001678.5	ENSP00000250111.4
ATP1B2	ENST00000577113.1	c.148-112C>T		intron_variant	Intron 1 of 5	3		ENSP00000460499.1
ATP1B2	ENST00000577026.5	c.307-112C>T		intron_variant	Intron 3 of 5	4		ENSP00000459145.1

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

African (AFR) AF: 0.283 AC: 7154 AN: 25318

American (AMR) AF: 0.486 AC: 20805 AN: 42774

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 11359 AN: 22424

East Asian (EAS) AF: 0.537 AC: 20170 AN: 37564

South Asian (SAS) AF: 0.372 AC: 27875 AN: 75016

European-Finnish (FIN) AF: 0.531 AC: 26625 AN: 50188

Middle Eastern (MID) AF: 0.484 AC: 2364 AN: 4886

European-Non Finnish (NFE) AF: 0.523 AC: 389177 AN: 743540

Other (OTH) AF: 0.502 AC: 23368 AN: 46548

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

African (AFR) AF: 0.285 AC: 11809 AN: 41406

American (AMR) AF: 0.479 AC: 7302 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 1750 AN: 3464

East Asian (EAS) AF: 0.574 AC: 2965 AN: 5162

South Asian (SAS) AF: 0.384 AC: 1841 AN: 4798

European-Finnish (FIN) AF: 0.538 AC: 5676 AN: 10556

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.528 AC: 35868 AN: 67918

Other (OTH) AF: 0.479 AC: 1009 AN: 2106

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
PhyloP100		-0.80
PromoterAI		0.022	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1642764; hg19: chr17-7557834; COSMIC: COSV51515227;