rs11805078

Positions:

• chr1-116381693-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000701.8(ATP1A1):​c.13-2321C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0839 in 152,174 control chromosomes in the GnomAD database, including 1,255 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 0.084 (1255 hom., cov: 32)
• Consequence: ATP1A1 NM_000701.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.457

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP1A1	NM_000701.8	c.13-2321C>T		intron_variant		ENST00000295598.10
ATP1A1	NM_001160233.2	c.13-2321C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP1A1	ENST00000295598.10	c.13-2321C>T		intron_variant		1	NM_000701.8	P4
ATP1A1-AS1	ENST00000675607.1	n.386-1648G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0837 AC: 12734 AN: 152056 Hom.: 1253 Cov.: 32

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0365

Gnomad ASJ AF: 0.00835

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0315

Gnomad FIN AF: 0.0119

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0268

Gnomad OTH AF: 0.0526

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0839 AC: 12760 AN: 152174 Hom.: 1255 Cov.: 32 AF XY: 0.0811 AC XY: 6032 AN XY: 74396

Gnomad4 AFR AF: 0.240

Gnomad4 AMR AF: 0.0365

Gnomad4 ASJ AF: 0.00835

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0311

Gnomad4 FIN AF: 0.0119

Gnomad4 NFE AF: 0.0267

Gnomad4 OTH AF: 0.0521

Alfa AF: 0.0578 Hom.: 71

Bravo AF: 0.0916

Asia WGS AF: 0.0250 AC: 88 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.3
DANN	Benign	0.62

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: rs11805078; hg19: chr1-116924315;