chr17-7654101-A-G

Variant names:

• chr17-7654101-A-G
• rs1642763
• NM_001678.5:c.396A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001678.5(ATP1B2):​c.396A>G​(p.Gly132Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.769 in 1,613,966 control chromosomes in the GnomAD database, including 478,665 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 0.80 (49011 hom., cov: 31)
  • Exomes 𝑓: 0.77 (429654 hom.)
• Consequence: ATP1B2 NM_001678.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.339
• Publications: 44 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP7: Synonymous conserved (PhyloP=-0.339 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.877 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.396A>G	p.Gly132Gly	synonymous	Exon 4 of 7	NP_001669.3
	ATP1B2	NM_001303263.2		c.150A>G	p.Gly50Gly	synonymous	Exon 3 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.396A>G	p.Gly132Gly	synonymous	Exon 4 of 7	ENSP00000250111.4
	ATP1B2	ENST00000577026.5	TSL:4	c.150A>G	p.Gly50Gly	synonymous	Exon 3 of 6	ENSP00000459145.1
	ATP1B2	ENST00000577113.1	TSL:3	c.-10A>G		upstream_gene	N/A	ENSP00000460499.1

Frequencies

GnomAD3 genomes AF: 0.800 AC: 121620 AN: 152002 Hom.: 48964 Cov.: 31

Gnomad AFR AF: 0.884

Gnomad AMI AF: 0.751

Gnomad AMR AF: 0.793

Gnomad ASJ AF: 0.774

Gnomad EAS AF: 0.659

Gnomad SAS AF: 0.754

Gnomad FIN AF: 0.762

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.772

Gnomad OTH AF: 0.810

GnomAD2 exomes AF: 0.768 AC: 193043 AN: 251452 AF XY: 0.768

Gnomad AFR exome AF: 0.887

Gnomad AMR exome AF: 0.771

Gnomad ASJ exome AF: 0.775

Gnomad EAS exome AF: 0.656

Gnomad FIN exome AF: 0.750

Gnomad NFE exome AF: 0.773

Gnomad OTH exome AF: 0.771

GnomAD4 exome AF: 0.766 AC: 1119532 AN: 1461846 Hom.: 429654 Cov.: 84 AF XY: 0.766 AC XY: 557352 AN XY: 727230

African (AFR) AF: 0.886 AC: 29674 AN: 33480

American (AMR) AF: 0.776 AC: 34727 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.776 AC: 20291 AN: 26136

East Asian (EAS) AF: 0.632 AC: 25086 AN: 39698

South Asian (SAS) AF: 0.760 AC: 65577 AN: 86256

European-Finnish (FIN) AF: 0.749 AC: 40030 AN: 53418

Middle Eastern (MID) AF: 0.881 AC: 5080 AN: 5768

European-Non Finnish (NFE) AF: 0.766 AC: 852091 AN: 1111970

Other (OTH) AF: 0.778 AC: 46976 AN: 60396

GnomAD4 genome AF: 0.800 AC: 121722 AN: 152120 Hom.: 49011 Cov.: 31 AF XY: 0.798 AC XY: 59369 AN XY: 74354

African (AFR) AF: 0.884 AC: 36710 AN: 41514

American (AMR) AF: 0.793 AC: 12104 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.774 AC: 2687 AN: 3470

East Asian (EAS) AF: 0.658 AC: 3404 AN: 5174

South Asian (SAS) AF: 0.755 AC: 3637 AN: 4820

European-Finnish (FIN) AF: 0.762 AC: 8058 AN: 10568

Middle Eastern (MID) AF: 0.932 AC: 274 AN: 294

European-Non Finnish (NFE) AF: 0.772 AC: 52467 AN: 67998

Other (OTH) AF: 0.806 AC: 1698 AN: 2108

Alfa AF: 0.782 Hom.: 147921

Bravo AF: 0.803

Asia WGS AF: 0.693 AC: 2412 AN: 3478

EpiCase AF: 0.785

EpiControl AF: 0.786

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	8.0
DANN	Benign	0.68
PhyloP100		-0.34
PromoterAI		-0.024	Neutral
Mutation Taster		=99/1	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: rs1642763; hg19: chr17-7557419; COSMIC: COSV51514774; COSMIC: COSV51514774;