Genetic Variant ATP1B2:c.-301T>G (chr17-7651218-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001678.5(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
NM_001678.5 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.95

Publications

3 publications found

Variant links:

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]

ATP1B2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ATP1B2	NM_001678.5 link	c.-301T>G		5_prime_UTR_variant	Exon 1 of 7	ENST00000250111.9	NP_001669.3	P14415
ATP1B2	NM_001303263.2 link	c.-5-2623T>G		intron_variant	Intron 1 of 5		NP_001290192.1	P14415

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP1B2	ENST00000250111.9 link	c.-301T>G		5_prime_UTR_variant	Exon 1 of 7	1	NM_001678.5	ENSP00000250111.4		P14415
ATP1B2	ENST00000577026.5 link	c.-5-2623T>G		intron_variant	Intron 1 of 5	4		ENSP00000459145.1		I3L1V9

Frequencies

GnomAD3 genomes

AF:

0.343

AC:

51958

AN:

151576

Hom.:

9707

Cov.:

show subpopulations

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.:

AF XY:

0.306

AC XY:

30465

AN XY:

99686

show subpopulations

African (AFR)

AF:

0.438

AC:

1243

AN:

2840

American (AMR)

AF:

0.183

AC:

1092

AN:

5976

Ashkenazi Jewish (ASJ)

AF:

0.303

AC:

1488

AN:

4908

East Asian (EAS)

AF:

0.161

AC:

1215

AN:

7538

South Asian (SAS)

AF:

0.392

AC:

12150

AN:

30998

European-Finnish (FIN)

AF:

0.202

AC:

2032

AN:

10048

Middle Eastern (MID)

AF:

0.330

AC:

243

AN:

736

European-Non Finnish (NFE)

AF:

0.285

AC:

31382

AN:

110232

Other (OTH)

AF:

0.293

AC:

3018

AN:

10288

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

1739

3478

5216

6955

8694

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.343

AC:

52043

AN:

151694

Hom.:

9744

Cov.:

AF XY:

0.338

AC XY:

25056

AN XY:

74130

show subpopulations

African (AFR)

AF:

0.493

AC:

20366

AN:

41282

American (AMR)

AF:

0.248

AC:

3782

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.335

AC:

1162

AN:

3470

East Asian (EAS)

AF:

0.190

AC:

973

AN:

5124

South Asian (SAS)

AF:

0.406

AC:

1951

AN:

4804

European-Finnish (FIN)

AF:

0.207

AC:

2187

AN:

10548

Middle Eastern (MID)

AF:

0.344

AC:

101

AN:

294

European-Non Finnish (NFE)

AF:

0.304

AC:

20612

AN:

67898

Other (OTH)

AF:

0.320

AC:

675

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

1598

3195

4793

6390

7988

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

(source)

DANN

Benign

0.16

PhyloP100

-1.9

PromoterAI

0.012

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

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17-7651218-T-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over