rs12079745

Positions:

• chr1-169131822-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001677.4(ATP1B1):​c.*267G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 448,764 control chromosomes in the GnomAD database, including 8,320 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 0.11 (2187 hom., cov: 32)
  • Exomes 𝑓: 0.13 (6133 hom.)
• Consequence: ATP1B1 NM_001677.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.43

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]

ATP1B1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP1B1	NM_001677.4	c.*267G>A		3_prime_UTR_variant	6/6	ENST00000367815.9	NP_001668.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP1B1	ENST00000367815.9	c.*267G>A		3_prime_UTR_variant	6/6	1	NM_001677.4	ENSP00000356789.3

Frequencies

GnomAD3 genomes AF: 0.112 AC: 17050 AN: 151996 Hom.: 2185 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.0330

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.734

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.0713

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.0601

Gnomad OTH AF: 0.118

GnomAD4 exome AF: 0.126 AC: 37278 AN: 296650 Hom.: 6133 Cov.: 4 AF XY: 0.130 AC XY: 20366 AN XY: 156490

Gnomad4 AFR exome AF: 0.109

Gnomad4 AMR exome AF: 0.136

Gnomad4 ASJ exome AF: 0.154

Gnomad4 EAS exome AF: 0.696

Gnomad4 SAS exome AF: 0.188

Gnomad4 FIN exome AF: 0.0693

Gnomad4 NFE exome AF: 0.0608

Gnomad4 OTH exome AF: 0.126

GnomAD4 genome AF: 0.112 AC: 17088 AN: 152114 Hom.: 2187 Cov.: 32 AF XY: 0.120 AC XY: 8886 AN XY: 74334

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.150

Gnomad4 EAS AF: 0.734

Gnomad4 SAS AF: 0.220

Gnomad4 FIN AF: 0.0713

Gnomad4 NFE AF: 0.0601

Gnomad4 OTH AF: 0.126

Alfa AF: 0.0833 Hom.: 107

Bravo AF: 0.119

Asia WGS AF: 0.441 AC: 1531 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	11
DANN	Benign	0.86
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs12079745; hg19: chr1-169101060;