NM_000701.8:c.1023+234T>A

Variant names:

• chr1-116389941-T-A
• rs850609
• NM_000701.8:c.1023+234T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.198
• Publications: 1 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000701.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP1A1	NM_000701.8	MANE Select	c.1023+234T>A		intron	N/A	NP_000692.2
	ATP1A1	NM_001160233.2		c.1023+234T>A		intron	N/A	NP_001153705.1
	ATP1A1	NM_001160234.2		c.930+234T>A		intron	N/A	NP_001153706.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP1A1	ENST00000295598.10	TSL:1 MANE Select	c.1023+234T>A		intron	N/A	ENSP00000295598.5
	ATP1A1	ENST00000537345.5	TSL:2	c.1023+234T>A		intron	N/A	ENSP00000445306.1
	ATP1A1	ENST00000369496.8	TSL:2	c.930+234T>A		intron	N/A	ENSP00000358508.4

Frequencies

GnomAD3 genomes AF: 0.807 AC: 122724 AN: 152062 Hom.: 50363 Cov.: 32

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.: 7 AF XY: 0.760 AC XY: 219570 AN XY: 289056

African (AFR) AF: 0.960 AC: 13710 AN: 14276

American (AMR) AF: 0.835 AC: 15854 AN: 18990

Ashkenazi Jewish (ASJ) AF: 0.684 AC: 9877 AN: 14444

East Asian (EAS) AF: 0.652 AC: 20673 AN: 31724

South Asian (SAS) AF: 0.827 AC: 38756 AN: 46870

European-Finnish (FIN) AF: 0.715 AC: 21214 AN: 29666

Middle Eastern (MID) AF: 0.734 AC: 1607 AN: 2188

European-Non Finnish (NFE) AF: 0.753 AC: 276692 AN: 367592

Other (OTH) AF: 0.752 AC: 22283 AN: 29628

GnomAD4 genome AF: 0.807 AC: 122858 AN: 152180 Hom.: 50434 Cov.: 32 AF XY: 0.803 AC XY: 59737 AN XY: 74394

African (AFR) AF: 0.955 AC: 39675 AN: 41554

American (AMR) AF: 0.828 AC: 12652 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.678 AC: 2352 AN: 3468

East Asian (EAS) AF: 0.613 AC: 3167 AN: 5170

South Asian (SAS) AF: 0.828 AC: 3996 AN: 4824

European-Finnish (FIN) AF: 0.698 AC: 7370 AN: 10558

Middle Eastern (MID) AF: 0.733 AC: 214 AN: 292

European-Non Finnish (NFE) AF: 0.750 AC: 51004 AN: 68002

Other (OTH) AF: 0.779 AC: 1647 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.6
DANN	Benign	0.51
PhyloP100		-0.20
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs850609; hg19: chr1-116932563;