chr1-116406090-G-A

Variant names:

• chr1-116406090-G-A
• rs850610
• ENST00000369491.2:n.345C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000369491.2(ATP1A1-AS1):​n.345C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 212,480 control chromosomes in the GnomAD database, including 33,788 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 0.50 (22876 hom., cov: 31)
  • Exomes 𝑓: 0.57 (10912 hom.)
• Consequence: ATP1A1-AS1 ENST00000369491.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.655
• Publications: 20 publications found

Genes affected

ATP1A1-AS1 (HGNC:28262): (ATP1A1 antisense RNA 1)

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 Gene-Disease associations (from GenCC):

• Charcot-Marie-tooth disease, axonal, type 2DD

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, ClinGen, Labcorp Genetics (formerly Invitae)
• hypomagnesemia, seizures, and intellectual disability 2

  Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Illumina
• neurodevelopmental disorder

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000369491.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP1A1-AS1	NR_024124.2		n.176C>T		non_coding_transcript_exon	Exon 2 of 2
	ATP1A1-AS1	NR_024125.2		n.452C>T		non_coding_transcript_exon	Exon 3 of 3
	ATP1A1-AS1	NR_024126.1		n.215C>T		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP1A1-AS1	ENST00000369491.2	TSL:1	n.345C>T		non_coding_transcript_exon	Exon 4 of 4
	ATP1A1-AS1	ENST00000369492.5	TSL:1	n.452C>T		non_coding_transcript_exon	Exon 3 of 3
	ATP1A1-AS1	ENST00000493908.2	TSL:1	n.178-4959C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75350 AN: 151800 Hom.: 22875 Cov.: 31

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.666

Gnomad AMR AF: 0.513

Gnomad ASJ AF: 0.568

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.726

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.680

Gnomad OTH AF: 0.531

GnomAD4 exome AF: 0.572 AC: 34612 AN: 60562 Hom.: 10912 Cov.: 0 AF XY: 0.580 AC XY: 17806 AN XY: 30706

African (AFR) AF: 0.118 AC: 405 AN: 3428

American (AMR) AF: 0.446 AC: 2330 AN: 5222

Ashkenazi Jewish (ASJ) AF: 0.544 AC: 655 AN: 1204

East Asian (EAS) AF: 0.255 AC: 1252 AN: 4916

South Asian (SAS) AF: 0.724 AC: 3684 AN: 5088

European-Finnish (FIN) AF: 0.616 AC: 9521 AN: 15464

Middle Eastern (MID) AF: 0.558 AC: 77 AN: 138

European-Non Finnish (NFE) AF: 0.673 AC: 15404 AN: 22880

Other (OTH) AF: 0.578 AC: 1284 AN: 2222

GnomAD4 genome AF: 0.496 AC: 75354 AN: 151918 Hom.: 22876 Cov.: 31 AF XY: 0.495 AC XY: 36728 AN XY: 74240

African (AFR) AF: 0.147 AC: 6104 AN: 41418

American (AMR) AF: 0.513 AC: 7826 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.568 AC: 1965 AN: 3462

East Asian (EAS) AF: 0.286 AC: 1469 AN: 5144

South Asian (SAS) AF: 0.726 AC: 3491 AN: 4810

European-Finnish (FIN) AF: 0.607 AC: 6398 AN: 10546

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.680 AC: 46207 AN: 67958

Other (OTH) AF: 0.532 AC: 1122 AN: 2110

Alfa AF: 0.617 Hom.: 71238

Bravo AF: 0.463

Asia WGS AF: 0.469 AC: 1632 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.4
DANN	Benign	0.78
PhyloP100		-0.66

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs850610; hg19: chr1-116948712; COSMIC: COSV55190134;