chr1-169130042-A-C

Variant names:

• chr1-169130042-A-C
• rs61803314
• NM_001677.4:c.600A>C

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001677.4(ATP1B1):​c.600A>C​(p.Pro200Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00865 in 1,614,048 control chromosomes in the GnomAD database, including 95 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0057 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0090 (91 hom.)
• Consequence: ATP1B1 NM_001677.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.93
• Publications: 1 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 1-169130042-A-C is Benign according to our data. Variant chr1-169130042-A-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 496144.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.93 with no splicing effect.
• BS2: High AC in GnomAd4 at 868 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.600A>C	p.Pro200Pro	synonymous	Exon 5 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.600A>C	p.Pro200Pro	synonymous	Exon 5 of 6	ENSP00000356789.3	P05026-1
	ATP1B1	ENST00000367816.5	TSL:5	c.600A>C	p.Pro200Pro	synonymous	Exon 6 of 7	ENSP00000356790.1	P05026-1
	ATP1B1	ENST00000689522.1		c.600A>C	p.Pro200Pro	synonymous	Exon 6 of 7	ENSP00000509039.1	P05026-1

Frequencies

GnomAD3 genomes AF: 0.00571 AC: 869 AN: 152198 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00166

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.00779

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00518

Gnomad FIN AF: 0.00320

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00998

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.00627 AC: 1576 AN: 251418 AF XY: 0.00671

Gnomad AFR exome AF: 0.00160

Gnomad AMR exome AF: 0.00194

Gnomad ASJ exome AF: 0.00982

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00319

Gnomad NFE exome AF: 0.00962

Gnomad OTH exome AF: 0.00717

GnomAD4 exome AF: 0.00896 AC: 13091 AN: 1461732 Hom.: 91 Cov.: 31 AF XY: 0.00888 AC XY: 6459 AN XY: 727158

African (AFR) AF: 0.00146 AC: 49 AN: 33480

American (AMR) AF: 0.00199 AC: 89 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0100 AC: 262 AN: 26130

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39682

South Asian (SAS) AF: 0.00547 AC: 472 AN: 86238

European-Finnish (FIN) AF: 0.00346 AC: 185 AN: 53412

Middle Eastern (MID) AF: 0.00313 AC: 18 AN: 5756

European-Non Finnish (NFE) AF: 0.0104 AC: 11531 AN: 1111924

Other (OTH) AF: 0.00802 AC: 484 AN: 60386

GnomAD4 genome AF: 0.00570 AC: 868 AN: 152316 Hom.: 4 Cov.: 32 AF XY: 0.00494 AC XY: 368 AN XY: 74488

African (AFR) AF: 0.00166 AC: 69 AN: 41568

American (AMR) AF: 0.00163 AC: 25 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00779 AC: 27 AN: 3468

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

South Asian (SAS) AF: 0.00518 AC: 25 AN: 4824

European-Finnish (FIN) AF: 0.00320 AC: 34 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00997 AC: 678 AN: 68022

Other (OTH) AF: 0.00473 AC: 10 AN: 2116

Alfa AF: 0.00799 Hom.: 3

Bravo AF: 0.00538

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.00905

EpiControl AF: 0.00978

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.35
DANN	Benign	0.65
PhyloP100		-1.9
Mutation Taster		=100/0	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: rs61803314; hg19: chr1-169099280;