Genetic Variant NM_001678.5:c.-301T>C (chr17-7651218-T-C) – 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>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

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=-0.82).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP1B2	NM_001678.5 link	c.-301T>C		5_prime_UTR_variant	Exon 1 of 7	ENST00000250111.9	NP_001669.3	P14415
ATP1B2	NM_001303263.2 link	c.-5-2623T>C		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>C		5_prime_UTR_variant	Exon 1 of 7	1	NM_001678.5	ENSP00000250111.4		P14415
ATP1B2	ENST00000577026.5 link	c.-5-2623T>C		intron_variant	Intron 1 of 5	4		ENSP00000459145.1		I3L1V9

Frequencies

GnomAD3 genomes

AF:

0.525

AC:

79663

AN:

151666

Hom.:

21498

Cov.:

show subpopulations

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.:

AF XY:

0.533

AC XY:

53157

AN XY:

99774

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

2101

4202

6302

8403

10504

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.525

AC:

79670

AN:

151784

Hom.:

21499

Cov.:

AF XY:

0.525

AC XY:

38927

AN XY:

74168

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1861

3722

5583

7444

9305

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

1754

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

5.1

(source)

DANN

Benign

0.15

PhyloP100

-1.9

PromoterAI

-0.044

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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NM_001678.5:c.-301T>C

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