17-7651218-T-C

Variant names:

• chr17-7651218-T-C
• rs1050528
• NM_001678.5:c.-301T>C

Variant summary

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

The NM_001678.5(ATP1B2):​c.-301T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 335,450 control chromosomes in the GnomAD database, including 49,885 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 0.52 (21499 hom., cov: 29)
  • Exomes 𝑓: 0.55 (28386 hom.)
• Consequence: ATP1B2 NM_001678.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.95
• Publications: 3 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.589 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.-301T>C		5_prime_UTR	Exon 1 of 7	NP_001669.3
	ATP1B2	NM_001303263.2		c.-5-2623T>C		intron	N/A	NP_001290192.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP1B2	ENST00000250111.9	TSL:1 MANE Select	c.-301T>C		5_prime_UTR	Exon 1 of 7	ENSP00000250111.4
	ATP1B2	ENST00000577026.5	TSL:4	c.-5-2623T>C		intron	N/A	ENSP00000459145.1

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79663 AN: 151666 Hom.: 21498 Cov.: 29

Gnomad AFR AF: 0.410

Gnomad AMI AF: 0.600

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.540

Gnomad EAS AF: 0.467

Gnomad SAS AF: 0.405

Gnomad FIN AF: 0.603

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.556

GnomAD4 exome AF: 0.547 AC: 100533 AN: 183666 Hom.: 28386 Cov.: 0 AF XY: 0.533 AC XY: 53157 AN XY: 99774

African (AFR) AF: 0.450 AC: 1288 AN: 2860

American (AMR) AF: 0.637 AC: 3807 AN: 5976

Ashkenazi Jewish (ASJ) AF: 0.558 AC: 2740 AN: 4908

East Asian (EAS) AF: 0.400 AC: 3014 AN: 7532

South Asian (SAS) AF: 0.407 AC: 12612 AN: 31002

European-Finnish (FIN) AF: 0.602 AC: 6054 AN: 10052

Middle Eastern (MID) AF: 0.581 AC: 431 AN: 742

European-Non Finnish (NFE) AF: 0.587 AC: 64716 AN: 110272

Other (OTH) AF: 0.569 AC: 5871 AN: 10322

GnomAD4 genome AF: 0.525 AC: 79670 AN: 151784 Hom.: 21499 Cov.: 29 AF XY: 0.525 AC XY: 38927 AN XY: 74168

African (AFR) AF: 0.409 AC: 16893 AN: 41334

American (AMR) AF: 0.600 AC: 9155 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.540 AC: 1873 AN: 3468

East Asian (EAS) AF: 0.467 AC: 2394 AN: 5128

South Asian (SAS) AF: 0.406 AC: 1953 AN: 4810

European-Finnish (FIN) AF: 0.603 AC: 6356 AN: 10540

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.577 AC: 39161 AN: 67918

Other (OTH) AF: 0.552 AC: 1166 AN: 2114

Alfa AF: 0.00 Hom.: 1754

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.1
DANN	Benign	0.15
PhyloP100		-1.9
PromoterAI		-0.044	Neutral
Mutation Taster		=300/0	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: rs1050528; hg19: chr17-7554536;