NM_001677.4:c.227-5175T>C

Variant names:

• chr1-169119709-T-C
• rs10919062
• NM_001677.4:c.227-5175T>C

Variant summary

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

The NM_001677.4(ATP1B1):​c.227-5175T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,226 control chromosomes in the GnomAD database, including 1,096 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 (1096 hom., cov: 32)
• Consequence: ATP1B1 NM_001677.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22
• Publications: 10 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001677.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP1B1	NM_001677.4	MANE Select	c.227-5175T>C		intron	N/A	NP_001668.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP1B1	ENST00000367815.9	TSL:1 MANE Select	c.227-5175T>C		intron	N/A	ENSP00000356789.3
	ATP1B1	ENST00000367816.5	TSL:5	c.227-5175T>C		intron	N/A	ENSP00000356790.1
	ATP1B1	ENST00000689522.1		c.227-5175T>C		intron	N/A	ENSP00000509039.1

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15815 AN: 152108 Hom.: 1094 Cov.: 32

Gnomad AFR AF: 0.0247

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.0295

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.142

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

GnomAD4 genome AF: 0.104 AC: 15814 AN: 152226 Hom.: 1096 Cov.: 32 AF XY: 0.106 AC XY: 7880 AN XY: 74422

African (AFR) AF: 0.0246 AC: 1023 AN: 41562

American (AMR) AF: 0.211 AC: 3223 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 384 AN: 3468

East Asian (EAS) AF: 0.0297 AC: 154 AN: 5180

South Asian (SAS) AF: 0.103 AC: 497 AN: 4822

European-Finnish (FIN) AF: 0.105 AC: 1111 AN: 10592

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.133 AC: 9030 AN: 68006

Other (OTH) AF: 0.140 AC: 296 AN: 2112

Alfa AF: 0.113 Hom.: 742

Bravo AF: 0.108

Asia WGS AF: 0.0630 AC: 221 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.0
DANN	Benign	0.45
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10919062; hg19: chr1-169088947;