1-169106936-G-C

Variant names:

• chr1-169106936-G-C
• rs1657604508
• NM_001677.4:c.97+10G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001677.4(ATP1B1):​c.97+10G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000704 in 1,419,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: ATP1B1 NM_001677.4 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.771
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).

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.97+10G>C		intron	N/A	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.97+10G>C		intron	N/A	ENSP00000356789.3	P05026-1
	ATP1B1	ENST00000367816.5	TSL:5	c.97+10G>C		intron	N/A	ENSP00000356790.1	P05026-1
	ATP1B1	ENST00000689522.1		c.97+10G>C		intron	N/A	ENSP00000509039.1	P05026-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 204572 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.04e-7 AC: 1 AN: 1419862 Hom.: 0 Cov.: 30 AF XY: 0.00000142 AC XY: 1 AN XY: 705804

African (AFR) AF: 0.00 AC: 0 AN: 29414

American (AMR) AF: 0.00 AC: 0 AN: 40228

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24910

East Asian (EAS) AF: 0.00 AC: 0 AN: 34738

South Asian (SAS) AF: 0.00 AC: 0 AN: 81826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4104

European-Non Finnish (NFE) AF: 9.14e-7 AC: 1 AN: 1093628

Other (OTH) AF: 0.00 AC: 0 AN: 58398

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	18
DANN	Benign	0.84
PhyloP100		0.77
PromoterAI		-0.034	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs1657604508; hg19: chr1-169076174;