dbSNP rs850609: ATP1A1:c.1023+234T>A (chr1-116389941-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000701.8(ATP1A1):c.1023+234T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.768 in 707,558 control chromosomes in the GnomAD database, including 210,782 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 0.81 ( 50434 hom., cov: 32)

Exomes 𝑓: 0.76 ( 160348 hom. )

Consequence

ATP1A1
NM_000701.8 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.198

Variant links:

Genes affected

ATP1A1 (HGNC:799): (ATPase Na+/K+ transporting subunit alpha 1) The protein encoded by this gene belongs to the family of P-type cation transport ATPases, 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 catalytic subunit of Na+/K+ -ATPase is encoded by multiple genes. This gene encodes an alpha 1 subunit. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]

ATP1A1 links:

ATP1A1-AS1 (HGNC:28262): (ATP1A1 antisense RNA 1)

ATP1A1-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.947 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ATP1A1	NM_000701.8 link	c.1023+234T>A	intron_variant	Intron 8 of 22	ENST00000295598.10	NP_000692.2	P05023-1
ATP1A1	NM_001160233.2 link	c.1023+234T>A	intron_variant	Intron 8 of 22		NP_001153705.1	P05023-4
ATP1A1	NM_001160234.2 link	c.930+234T>A	intron_variant	Intron 8 of 22		NP_001153706.1	P05023-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP1A1	ENST00000295598.10 link	c.1023+234T>A		intron_variant	Intron 8 of 22	1	NM_000701.8	ENSP00000295598.5		P05023-1

Frequencies

GnomAD3 genomes

AF:

0.807

AC:

122724

AN:

152062

Hom.:

50363

Cov.:

show subpopulations

Gnomad AFR

AF:

0.955

Gnomad AMI

AF:

0.856

Gnomad AMR

AF:

0.828

Gnomad ASJ

AF:

0.678

Gnomad EAS

AF:

0.613

Gnomad SAS

AF:

0.829

Gnomad FIN

AF:

0.698

Gnomad MID

AF:

0.717

Gnomad NFE

AF:

0.750

Gnomad OTH

AF:

0.775

GnomAD4 exome

AF:

0.757

AC:

420666

AN:

555378

Hom.:

160348

Cov.:

AF XY:

0.760

AC XY:

219570

AN XY:

289056

show subpopulations

Gnomad4 AFR exome

AF:

0.960

Gnomad4 AMR exome

AF:

0.835

Gnomad4 ASJ exome

AF:

0.684

Gnomad4 EAS exome

AF:

0.652

Gnomad4 SAS exome

AF:

0.827

Gnomad4 FIN exome

AF:

0.715

Gnomad4 NFE exome

AF:

0.753

Gnomad4 OTH exome

AF:

0.752

GnomAD4 genome

AF:

0.807

AC:

122858

AN:

152180

Hom.:

50434

Cov.:

AF XY:

0.803

AC XY:

59737

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.955

Gnomad4 AMR

AF:

0.828

Gnomad4 ASJ

AF:

0.678

Gnomad4 EAS

AF:

0.613

Gnomad4 SAS

AF:

0.828

Gnomad4 FIN

AF:

0.698

Gnomad4 NFE

AF:

0.750

Gnomad4 OTH

AF:

0.779

Alfa

AF:

0.776

Hom.:

5746

Bravo

AF:

0.820

Asia WGS

AF:

0.745

AC:

2593

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

1.6

DANN

Benign

0.51

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over