chr17-7651218-T-G

Position:

• chr17-7651218-T-G

Variant summary

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

The ENST00000250111.9(ATP1B2):​c.-301T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 335,258 control chromosomes in the GnomAD database, including 17,940 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 0.34 (9744 hom., cov: 29)
  • Exomes 𝑓: 0.29 (8196 hom.)
• Consequence: ATP1B2 ENST00000250111.9 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.95

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP1B2	NM_001678.5	c.-301T>G		5_prime_UTR_variant	1/7	ENST00000250111.9	NP_001669.3
ATP1B2	NM_001303263.2	c.-5-2623T>G		intron_variant			NP_001290192.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP1B2	ENST00000250111.9	c.-301T>G		5_prime_UTR_variant	1/7	1	NM_001678.5	ENSP00000250111	P1
ATP1B2	ENST00000577026.5	c.-5-2623T>G		intron_variant		4		ENSP00000459145

Frequencies

GnomAD3 genomes AF: 0.343 AC: 51958 AN: 151576 Hom.: 9707 Cov.: 29

Gnomad AFR AF: 0.492

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.320

GnomAD4 exome AF: 0.293 AC: 53863 AN: 183564 Hom.: 8196 Cov.: 0 AF XY: 0.306 AC XY: 30465 AN XY: 99686

Gnomad4 AFR exome AF: 0.438

Gnomad4 AMR exome AF: 0.183

Gnomad4 ASJ exome AF: 0.303

Gnomad4 EAS exome AF: 0.161

Gnomad4 SAS exome AF: 0.392

Gnomad4 FIN exome AF: 0.202

Gnomad4 NFE exome AF: 0.285

Gnomad4 OTH exome AF: 0.293

GnomAD4 genome AF: 0.343 AC: 52043 AN: 151694 Hom.: 9744 Cov.: 29 AF XY: 0.338 AC XY: 25056 AN XY: 74130

Gnomad4 AFR AF: 0.493

Gnomad4 AMR AF: 0.248

Gnomad4 ASJ AF: 0.335

Gnomad4 EAS AF: 0.190

Gnomad4 SAS AF: 0.406

Gnomad4 FIN AF: 0.207

Gnomad4 NFE AF: 0.304

Gnomad4 OTH AF: 0.320

Alfa AF: 0.571 Hom.: 1754

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.4
DANN	Benign	0.16

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

Publications

LitVar

Other links and lift over

dbSNP: rs1050528; hg19: chr17-7554536;