rs10919071

Positions:

• chr1-169130245-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001677.4(ATP1B1):​c.648+155A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 152,276 control chromosomes in the GnomAD database, including 1,069 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 0.10 (1069 hom., cov: 32)
• Consequence: ATP1B1 NM_001677.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36

Genes affected

ATP1B1 (HGNC:804): (ATPase Na+/K+ transporting subunit beta 1) The protein encoded by this gene belongs to the family of Na+/K+ and H+/K+ ATPases beta chain proteins, 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 beta subunit regulates, through assembly of alpha/beta heterodimers, the number of sodium pumps transported to the plasma membrane. The glycoprotein subunit of Na+/K+ -ATPase is encoded by multiple genes. This gene encodes a beta 1 subunit. Alternatively spliced transcript variants encoding different isoforms have been described, but their biological validity is not known. [provided by RefSeq, Mar 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP1B1	NM_001677.4	c.648+155A>G		intron_variant		ENST00000367815.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP1B1	ENST00000367815.9	c.648+155A>G		intron_variant		1	NM_001677.4	P1

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15645 AN: 152158 Hom.: 1068 Cov.: 32

Gnomad AFR AF: 0.0245

Gnomad AMI AF: 0.0659

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.0283

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.138

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

GnomAD4 genome AF: 0.103 AC: 15641 AN: 152276 Hom.: 1069 Cov.: 32 AF XY: 0.105 AC XY: 7806 AN XY: 74462

Gnomad4 AFR AF: 0.0244

Gnomad4 AMR AF: 0.208

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.0285

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.104

Gnomad4 NFE AF: 0.131

Gnomad4 OTH AF: 0.136

Alfa AF: 0.122 Hom.: 1879

Bravo AF: 0.106

Asia WGS AF: 0.0630 AC: 221 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.0080
DANN	Benign	0.77

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: rs10919071; hg19: chr1-169099483; COSMIC: COSV63167138; COSMIC: COSV63167138;