17-7650425-G-C

Variant names:

• chr17-7650425-G-C
• rs1624085
• NM_001303263.2:c.-5-3416G>C

Variant summary

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

The NM_001303263.2(ATP1B2):​c.-5-3416G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 151,930 control chromosomes in the GnomAD database, including 18,416 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 0.46 (18416 hom., cov: 31)
• Consequence: ATP1B2 NM_001303263.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.111
• 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=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001303263.2. 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_001303263.2		c.-5-3416G>C		intron	N/A	NP_001290192.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP1B2	ENST00000577026.5	TSL:4	c.-5-3416G>C		intron	N/A	ENSP00000459145.1

Frequencies

GnomAD3 genomes AF: 0.461 AC: 69982 AN: 151812 Hom.: 18416 Cov.: 31

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.600

Gnomad AMR AF: 0.572

Gnomad ASJ AF: 0.517

Gnomad EAS AF: 0.460

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.603

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.503

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.461 AC: 69978 AN: 151930 Hom.: 18416 Cov.: 31 AF XY: 0.464 AC XY: 34431 AN XY: 74274

African (AFR) AF: 0.193 AC: 8002 AN: 41446

American (AMR) AF: 0.572 AC: 8739 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.517 AC: 1791 AN: 3466

East Asian (EAS) AF: 0.460 AC: 2363 AN: 5142

South Asian (SAS) AF: 0.404 AC: 1946 AN: 4814

European-Finnish (FIN) AF: 0.603 AC: 6380 AN: 10576

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.574 AC: 38994 AN: 67902

Other (OTH) AF: 0.499 AC: 1051 AN: 2106

Alfa AF: 0.504 Hom.: 2522

Bravo AF: 0.448

Asia WGS AF: 0.425 AC: 1477 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	12
DANN	Benign	0.78
PhyloP100		0.11
PromoterAI		-0.031	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1624085; hg19: chr17-7553743; COSMIC: COSV51515215;