chr17-7647235-C-T

Variant names:

• chr17-7647235-C-T
• rs1619016
• NM_001303263.2:c.-6+534C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001303263.2(ATP1B2):​c.-6+534C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.756 in 152,080 control chromosomes in the GnomAD database, including 45,318 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 0.76 (45318 hom., cov: 31)
• Consequence: ATP1B2 NM_001303263.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26

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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.872 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP1B2	NM_001303263.2	c.-6+534C>T		intron_variant	Intron 1 of 5		NP_001290192.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP1B2	ENST00000577026.5	c.-6+534C>T		intron_variant	Intron 1 of 5	4		ENSP00000459145.1

Frequencies

GnomAD3 genomes AF: 0.756 AC: 114927 AN: 151962 Hom.: 45321 Cov.: 31

Gnomad AFR AF: 0.516

Gnomad AMI AF: 0.856

Gnomad AMR AF: 0.803

Gnomad ASJ AF: 0.868

Gnomad EAS AF: 0.655

Gnomad SAS AF: 0.810

Gnomad FIN AF: 0.810

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.878

Gnomad OTH AF: 0.796

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

GnomAD4 genome AF: 0.756 AC: 114963 AN: 152080 Hom.: 45318 Cov.: 31 AF XY: 0.755 AC XY: 56133 AN XY: 74334

Gnomad4 AFR AF: 0.516

Gnomad4 AMR AF: 0.802

Gnomad4 ASJ AF: 0.868

Gnomad4 EAS AF: 0.654

Gnomad4 SAS AF: 0.810

Gnomad4 FIN AF: 0.810

Gnomad4 NFE AF: 0.878

Gnomad4 OTH AF: 0.792

Alfa AF: 0.860 Hom.: 71347

Bravo AF: 0.744

Asia WGS AF: 0.708 AC: 2462 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.6
DANN	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1619016; hg19: chr17-7550553;