chr1-169130042-A-C

Position:

chr1-169130042-A-C

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001677.4(ATP1B1):c.600A>C(p.Pro200=) 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

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.93

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP1B1	NM_001677.4 linkuse as main transcript	c.600A>C	p.Pro200=	synonymous_variant	5/6	ENST00000367815.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP1B1	ENST00000367815.9 linkuse as main transcript	c.600A>C	p.Pro200=	synonymous_variant	5/6	1	NM_001677.4	P1	P05026-1

Frequencies

GnomAD3 genomes

AF:

0.00571

AC:

869

AN:

152198

Hom.:

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.00627

AC:

1576

AN:

251418

Hom.:

AF XY:

0.00671

AC XY:

912

AN XY:

135880

show subpopulations

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 SAS exome

AF:

0.00578

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.:

Cov.:

AF XY:

0.00888

AC XY:

6459

AN XY:

727158

show subpopulations

Gnomad4 AFR exome

AF:

0.00146

Gnomad4 AMR exome

AF:

0.00199

Gnomad4 ASJ exome

AF:

0.0100

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00547

Gnomad4 FIN exome

AF:

0.00346

Gnomad4 NFE exome

AF:

0.0104

Gnomad4 OTH exome

AF:

0.00802

GnomAD4 genome

AF:

0.00570

AC:

868

AN:

152316

Hom.:

Cov.:

AF XY:

0.00494

AC XY:

368

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00166

Gnomad4 AMR

AF:

0.00163

Gnomad4 ASJ

AF:

0.00779

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00518

Gnomad4 FIN

AF:

0.00320

Gnomad4 NFE

AF:

0.00997

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00799

Hom.:

Bravo

AF:

0.00538

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00905

EpiControl

AF:

0.00978

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	ATP1B1: BP4, BP7, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Feb 13, 2017	Variant summary: The ATP1B1 c.600A>C (p.Pro200Pro) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. Mutation taster predicts a benign outcome for this variant along with 5/5 splice prediction tools predicting the variant not to have an impact on normal splicing. This variant was found in 830/121356 control chromosomes (6 homozygotes) at a frequency of 0.0068394, which greatly exceeds the estimated maximal expected allele frequency of a pathogenic ATP1B1 variant (0.00001), suggesting this variant is likely a benign polymorphism. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.35

DANN

Benign

0.65

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over