chr1-116383811-G-A

Position:

• chr1-116383811-G-A

Variant summary

Our verdict is Benign. Variant got -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

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP1A1	NM_000701.8	c.13-203G>A		intron_variant		ENST00000295598.10	NP_000692.2
ATP1A1	NM_001160233.2	c.13-203G>A		intron_variant			NP_001153705.1
ATP1A1	NM_001160234.2	c.-81-203G>A		intron_variant			NP_001153706.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP1A1	ENST00000295598.10	c.13-203G>A		intron_variant		1	NM_000701.8	ENSP00000295598	P4
ATP1A1-AS1	ENST00000675607.1	n.386-3766C>T		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.246

Gnomad4 AMR AF: 0.0803

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.0337

Gnomad4 SAS AF: 0.00498

Gnomad4 FIN AF: 0.00330

Gnomad4 NFE AF: 0.00209

Gnomad4 OTH AF: 0.0572

Alfa AF: 0.0487 Hom.: 110

Bravo AF: 0.0946

Asia WGS AF: 0.0390 AC: 136 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 11, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.040
DANN	Benign	0.43

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: rs10924075; hg19: chr1-116926433;