rs769851426

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001677.4(ATP1B1):c.382G>A(p.Asp128Asn) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000423 in 1,608,322 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/24 in silico tools predict a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D128Y) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000045 ( 0 hom. )

Consequence

ATP1B1
NM_001677.4 missense, splice_region

Scores

Splicing: ADA: 0.5578

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.60

Publications

1 publications found

Variant links:

Genes affected

ATP1B1 (HGNC:804): (ATPase Na+/K+ transporting subunit beta 1) 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 1 subunit. Alternatively spliced transcript variants encoding different isoforms have been described, but their biological validity is not known. [provided by RefSeq, Mar 2010]

ATP1B1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.024336815).

BP6

Variant 1-169125039-G-A is Benign according to our data. Variant chr1-169125039-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1331399.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAdExome4 at 65 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001677.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP1B1	NM_001677.4	MANE Select	c.382G>A	p.Asp128Asn	missense splice_region	Exon 3 of 6	NP_001668.1	A3KLL5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATP1B1	ENST00000367815.9	TSL:1 MANE Select	c.382G>A	p.Asp128Asn	missense splice_region	Exon 3 of 6	ENSP00000356789.3	P05026-1
ATP1B1	ENST00000367816.5	TSL:5	c.382G>A	p.Asp128Asn	missense splice_region	Exon 4 of 7	ENSP00000356790.1	P05026-1
ATP1B1	ENST00000689522.1		c.382G>A	p.Asp128Asn	missense splice_region	Exon 4 of 7	ENSP00000509039.1	P05026-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152036

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000150

AC:

AN:

246098

AF XY:

0.000105

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00109

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000892

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000446

AC:

AN:

1456168

Hom.:

Cov.:

AF XY:

0.0000345

AC XY:

AN XY:

724130

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33200

American (AMR)

AF:

0.000849

AC:

AN:

43606

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25952

East Asian (EAS)

AF:

0.00

AC:

AN:

39478

South Asian (SAS)

AF:

0.0000118

AC:

AN:

84944

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53358

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5746

European-Non Finnish (NFE)

AF:

0.0000189

AC:

AN:

1109724

Other (OTH)

AF:

0.0000997

AC:

AN:

60160

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152154

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41506

American (AMR)

AF:

0.000131

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4796

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67996

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000681

Hom.:

Bravo

AF:

0.0000453

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.000132

AC:

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.74

CADD

Benign

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.15

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.51

M_CAP

Benign

0.012

MetaRNN

Benign

0.024

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

PhyloP100

1.6

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.2

REVEL

Benign

0.074

Sift

Benign

0.47

Sift4G

Benign

0.40

Polyphen

0.0

Vest4

0.12

MutPred

0.45

Gain of catalytic residue at D128 (P = 0.0207)

MVP

0.47

MPC

0.77

ClinPred

0.022

GERP RS

1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Varity_R

0.034

gMVP

0.47

Mutation Taster

=86/14

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.56

dbscSNV1_RF

Pathogenic

0.72

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over