NM_000701.8:c.13-2321C>T

Variant names:

• chr1-116381693-C-T
• rs11805078
• NM_000701.8:c.13-2321C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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=-0.81).
• 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 rank	MANE	Protein	UniProt
ATP1A1	NM_000701.8	c.13-2321C>T		intron_variant	Intron 1 of 22	ENST00000295598.10	NP_000692.2
ATP1A1	NM_001160233.2	c.13-2321C>T		intron_variant	Intron 1 of 22		NP_001153705.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP1A1	ENST00000295598.10	c.13-2321C>T		intron_variant	Intron 1 of 22	1	NM_000701.8	ENSP00000295598.5

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

African (AFR) AF: 0.240 AC: 9943 AN: 41460

American (AMR) AF: 0.0365 AC: 558 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00835 AC: 29 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5182

South Asian (SAS) AF: 0.0311 AC: 150 AN: 4820

European-Finnish (FIN) AF: 0.0119 AC: 126 AN: 10606

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0267 AC: 1819 AN: 68022

Other (OTH) AF: 0.0521 AC: 110 AN: 2112

Alfa AF: 0.0643 Hom.: 92

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
PhyloP100		0.46
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: rs11805078; hg19: chr1-116924315;