chr1-169124978-G-A

Variant names:

• chr1-169124978-G-A
• rs61742560
• NM_001677.4:c.321G>A

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_001677.4(ATP1B1):​c.321G>A​(p.Arg107Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00916 in 1,613,900 control chromosomes in the GnomAD database, including 81 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0069 (8 hom., cov: 32)
  • Exomes 𝑓: 0.0094 (73 hom.)
• Consequence: ATP1B1 NM_001677.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0880
• Publications: 4 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 1-169124978-G-A is Benign according to our data. Variant chr1-169124978-G-A is described in ClinVar as Benign. ClinVar VariationId is 769250.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.088 with no splicing effect.
• BS2: High AC in GnomAd4 at 1047 AD gene.

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.321G>A	p.Arg107Arg	synonymous	Exon 3 of 6	NP_001668.1	A3KLL5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP1B1	ENST00000367815.9	TSL:1 MANE Select	c.321G>A	p.Arg107Arg	synonymous	Exon 3 of 6	ENSP00000356789.3	P05026-1
	ATP1B1	ENST00000367816.5	TSL:5	c.321G>A	p.Arg107Arg	synonymous	Exon 4 of 7	ENSP00000356790.1	P05026-1
	ATP1B1	ENST00000689522.1		c.321G>A	p.Arg107Arg	synonymous	Exon 4 of 7	ENSP00000509039.1	P05026-1

Frequencies

GnomAD3 genomes AF: 0.00688 AC: 1047 AN: 152158 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.00193

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.00975

Gnomad ASJ AF: 0.00893

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00974

Gnomad FIN AF: 0.00170

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0102

Gnomad OTH AF: 0.0105

GnomAD2 exomes AF: 0.00698 AC: 1753 AN: 251004 AF XY: 0.00773

Gnomad AFR exome AF: 0.00172

Gnomad AMR exome AF: 0.00491

Gnomad ASJ exome AF: 0.00735

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00180

Gnomad NFE exome AF: 0.0100

Gnomad OTH exome AF: 0.00752

GnomAD4 exome AF: 0.00940 AC: 13742 AN: 1461624 Hom.: 73 Cov.: 32 AF XY: 0.00947 AC XY: 6884 AN XY: 727106

African (AFR) AF: 0.00182 AC: 61 AN: 33468

American (AMR) AF: 0.00537 AC: 240 AN: 44654

Ashkenazi Jewish (ASJ) AF: 0.00719 AC: 188 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.00864 AC: 745 AN: 86206

European-Finnish (FIN) AF: 0.00212 AC: 113 AN: 53420

Middle Eastern (MID) AF: 0.00468 AC: 27 AN: 5764

European-Non Finnish (NFE) AF: 0.0107 AC: 11880 AN: 1111918

Other (OTH) AF: 0.00808 AC: 488 AN: 60388

GnomAD4 genome AF: 0.00688 AC: 1047 AN: 152276 Hom.: 8 Cov.: 32 AF XY: 0.00680 AC XY: 506 AN XY: 74440

African (AFR) AF: 0.00193 AC: 80 AN: 41548

American (AMR) AF: 0.00974 AC: 149 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00893 AC: 31 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00975 AC: 47 AN: 4820

European-Finnish (FIN) AF: 0.00170 AC: 18 AN: 10612

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0102 AC: 694 AN: 68026

Other (OTH) AF: 0.0104 AC: 22 AN: 2112

Alfa AF: 0.00707 Hom.: 2

Bravo AF: 0.00701

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.0111

EpiControl AF: 0.0103

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	8.8
DANN	Benign	0.59
PhyloP100		-0.088
Mutation Taster		=95/5	polymorphism

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: rs61742560; hg19: chr1-169094216; COSMIC: COSV100891648;