chr17-7650425-G-C

Position:

• chr17-7650425-G-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP1B2	NM_001303263.2	c.-5-3416G>C		intron_variant			NP_001290192.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP1B2	ENST00000577026.5	c.-5-3416G>C		intron_variant		4		ENSP00000459145

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

Gnomad4 AFR AF: 0.193

Gnomad4 AMR AF: 0.572

Gnomad4 ASJ AF: 0.517

Gnomad4 EAS AF: 0.460

Gnomad4 SAS AF: 0.404

Gnomad4 FIN AF: 0.603

Gnomad4 NFE AF: 0.574

Gnomad4 OTH AF: 0.499

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	12
DANN	Benign	0.78

Splicing

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

Publications

LitVar

Other links and lift over

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