1-116383811-G-A

Variant names:

• chr1-116383811-G-A
• rs10924075
• NM_000701.8:c.13-203G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000701.8(ATP1A1):​c.13-203G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0786 in 152,214 control chromosomes in the GnomAD database, including 1,377 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.079 (1377 hom., cov: 32)
• Consequence: ATP1A1 NM_000701.8 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.47
• Publications: 0 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 1-116383811-G-A is Benign according to our data. Variant chr1-116383811-G-A is described in ClinVar as Benign. ClinVar VariationId is 1251879.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.242 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP1A1	NM_000701.8	MANE Select	c.13-203G>A		intron	N/A	NP_000692.2
	ATP1A1	NM_001160233.2		c.13-203G>A		intron	N/A	NP_001153705.1	P05023-4
	ATP1A1	NM_001160234.2		c.-81-203G>A		intron	N/A	NP_001153706.1	P05023-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP1A1	ENST00000295598.10	TSL:1 MANE Select	c.13-203G>A		intron	N/A	ENSP00000295598.5	P05023-1
	ATP1A1	ENST00000897942.1		c.13-203G>A		intron	N/A	ENSP00000568001.1
	ATP1A1	ENST00000945201.1		c.13-203G>A		intron	N/A	ENSP00000615260.1

Frequencies

GnomAD3 genomes AF: 0.0783 AC: 11908 AN: 152096 Hom.: 1363 Cov.: 32

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0804

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.0337

Gnomad SAS AF: 0.00539

Gnomad FIN AF: 0.00330

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.00209

Gnomad OTH AF: 0.0583

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

GnomAD4 genome AF: 0.0786 AC: 11957 AN: 152214 Hom.: 1377 Cov.: 32 AF XY: 0.0771 AC XY: 5736 AN XY: 74436

African (AFR) AF: 0.246 AC: 10207 AN: 41496

American (AMR) AF: 0.0803 AC: 1229 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3472

East Asian (EAS) AF: 0.0337 AC: 175 AN: 5186

South Asian (SAS) AF: 0.00498 AC: 24 AN: 4824

European-Finnish (FIN) AF: 0.00330 AC: 35 AN: 10602

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.00209 AC: 142 AN: 68016

Other (OTH) AF: 0.0572 AC: 121 AN: 2116

Alfa AF: 0.0487 Hom.: 110

Bravo AF: 0.0946

Asia WGS AF: 0.0390 AC: 136 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.040
DANN	Benign	0.43
PhyloP100		-2.5
PromoterAI		-0.022	Neutral
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: rs10924075; hg19: chr1-116926433;