1-116374023-CT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000701.8(ATP1A1):c.12+501del variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.92 (64302 hom., cov: 0)
  • Exomes 𝑓: 0.89 (498262 hom.)
• Consequence: ATP1A1 NM_000701.8 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 1-116374023-CT-C is Benign according to our data. Variant chr1-116374023-CT-C is described in ClinVar as [Benign]. Clinvar id is 1280079.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP1A1	NM_000701.8	c.12+501del		intron_variant		ENST00000295598.10
ATP1A1	NM_001160233.2	c.-206del		5_prime_UTR_variant	1/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP1A1	ENST00000295598.10	c.12+501del		intron_variant		1	NM_000701.8	P4
ATP1A1	ENST00000537345.5	c.-206del		5_prime_UTR_variant	1/23	2		A1
ATP1A1	ENST00000418797.5	c.-82+1103del		intron_variant		3
ATP1A1	ENST00000488733.1	n.255+501del		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.918 AC: 139642 AN: 152072 Hom.: 64247 Cov.: 0

Gnomad AFR AF: 0.978

Gnomad AMI AF: 0.965

Gnomad AMR AF: 0.893

Gnomad ASJ AF: 0.896

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.919

Gnomad FIN AF: 0.931

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.881

Gnomad OTH AF: 0.895

GnomAD4 exome AF: 0.890 AC: 1118553 AN: 1257048 Hom.: 498262 Cov.: 0 AF XY: 0.890 AC XY: 541927 AN XY: 608910

Gnomad4 AFR exome AF: 0.984

Gnomad4 AMR exome AF: 0.878

Gnomad4 ASJ exome AF: 0.898

Gnomad4 EAS exome AF: 0.988

Gnomad4 SAS exome AF: 0.907

Gnomad4 FIN exome AF: 0.928

Gnomad4 NFE exome AF: 0.881

Gnomad4 OTH exome AF: 0.902

GnomAD4 genome AF: 0.918 AC: 139754 AN: 152188 Hom.: 64302 Cov.: 0 AF XY: 0.921 AC XY: 68486 AN XY: 74396

Gnomad4 AFR AF: 0.978

Gnomad4 AMR AF: 0.893

Gnomad4 ASJ AF: 0.896

Gnomad4 EAS AF: 0.995

Gnomad4 SAS AF: 0.918

Gnomad4 FIN AF: 0.931

Gnomad4 NFE AF: 0.881

Gnomad4 OTH AF: 0.897

Alfa AF: 0.879 Hom.: 2670

Bravo AF: 0.918

Asia WGS AF: 0.951 AC: 3306 AN: 3474

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 10, 2021

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Computational scores

Source: dbNSFP v4.3

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: rs11289194; hg19: chr1-116916645; COSMIC: COSV55189329;