Variant chr1-169124978-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_001677.4(ATP1B1):c.321G>A(p.Arg107=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00916 in 1,613,900 control chromosomes in the GnomAD database, including 81 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0069 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0094 ( 73 hom. )

Consequence

ATP1B1
NM_001677.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0880

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 1-169124978-G-A is Benign according to our data. Variant chr1-169124978-G-A is described in ClinVar as [Benign]. Clinvar id is 769250.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.088 with no splicing effect.

BS2

High AC in GnomAd4 at 1047 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP1B1	NM_001677.4 linkuse as main transcript	c.321G>A	p.Arg107=	synonymous_variant	3/6	ENST00000367815.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP1B1	ENST00000367815.9 linkuse as main transcript	c.321G>A	p.Arg107=	synonymous_variant	3/6	1	NM_001677.4	P1	P05026-1

Frequencies

GnomAD3 genomes

AF:

0.00688

AC:

1047

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00193

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.00975

Gnomad ASJ

AF:

0.00893

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00974

Gnomad FIN

AF:

0.00170

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0102

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.00698

AC:

1753

AN:

251004

Hom.:

AF XY:

0.00773

AC XY:

1048

AN XY:

135648

show subpopulations

Gnomad AFR exome

AF:

0.00172

Gnomad AMR exome

AF:

0.00491

Gnomad ASJ exome

AF:

0.00735

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00858

Gnomad FIN exome

AF:

0.00180

Gnomad NFE exome

AF:

0.0100

Gnomad OTH exome

AF:

0.00752

GnomAD4 exome

AF:

0.00940

AC:

13742

AN:

1461624

Hom.:

Cov.:

AF XY:

0.00947

AC XY:

6884

AN XY:

727106

show subpopulations

Gnomad4 AFR exome

AF:

0.00182

Gnomad4 AMR exome

AF:

0.00537

Gnomad4 ASJ exome

AF:

0.00719

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00864

Gnomad4 FIN exome

AF:

0.00212

Gnomad4 NFE exome

AF:

0.0107

Gnomad4 OTH exome

AF:

0.00808

GnomAD4 genome

AF:

0.00688

AC:

1047

AN:

152276

Hom.:

Cov.:

AF XY:

0.00680

AC XY:

506

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.00193

Gnomad4 AMR

AF:

0.00974

Gnomad4 ASJ

AF:

0.00893

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00975

Gnomad4 FIN

AF:

0.00170

Gnomad4 NFE

AF:

0.0102

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.00707

Hom.:

Bravo

AF:

0.00701

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.0111

EpiControl

AF:

0.0103

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2024	ATP1B1: BP4, BP7, BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

8.8

DANN

Benign

0.59

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over