1-169124978-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0880

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]

ACMG classification

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 GnomAd at 1047 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP1B1	NM_001677.4	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	c.321G>A	p.Arg107=	synonymous_variant	3/6	1	NM_001677.4	P1

Frequencies

GnomAD3 genomes AF: 0.00688 AC: 1047 AN: 152158 Hom.: 8 Cov.: 32

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.: 10 AF XY: 0.00773 AC XY: 1048 AN XY: 135648

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.: 73 Cov.: 32 AF XY: 0.00947 AC XY: 6884 AN XY: 727106

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.: 8 Cov.: 32 AF XY: 0.00680 AC XY: 506 AN XY: 74440

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.: 2

Bravo AF: 0.00701

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.0111

EpiControl AF: 0.0103

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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	Invitae	Dec 31, 2019	- -

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

Other links and lift over

dbSNP: rs61742560; hg19: chr1-169094216; COSMIC: COSV100891648;