1-203683210-C-T

Position:

chr1-203683210-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000357681.10(ATP2B4):c.5C>T(p.Thr2Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000473 in 1,613,070 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00051 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00047 ( 5 hom. )

Consequence

ATP2B4
ENST00000357681.10 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.17

Variant links:

Genes affected

ATP2B4 (HGNC:817): (ATPase plasma membrane Ca2+ transporting 4) The protein encoded by this gene belongs to the family of P-type primary ion transport ATPases characterized by the formation of an aspartyl phosphate intermediate during the reaction cycle. These enzymes remove bivalent calcium ions from eukaryotic cells against very large concentration gradients and play a critical role in intracellular calcium homeostasis. The mammalian plasma membrane calcium ATPase isoforms are encoded by at least four separate genes and the diversity of these enzymes is further increased by alternative splicing of transcripts. The expression of different isoforms and splice variants is regulated in a developmental, tissue- and cell type-specific manner, suggesting that these pumps are functionally adapted to the physiological needs of particular cells and tissues. This gene encodes the plasma membrane calcium ATPase isoform 4. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ATP2B4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010277808).

BP6

Variant 1-203683210-C-T is Benign according to our data. Variant chr1-203683210-C-T is described in ClinVar as [Benign]. Clinvar id is 1626186.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 77 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ATP2B4	NM_001684.5 linkuse as main transcript	c.5C>T	p.Thr2Met	missense_variant	2/21	ENST00000357681.10	NP_001675.3
ATP2B4	NM_001001396.3 linkuse as main transcript	c.5C>T	p.Thr2Met	missense_variant	2/22		NP_001001396.1
ATP2B4	NM_001365783.2 linkuse as main transcript	c.5C>T	p.Thr2Met	missense_variant	2/21		NP_001352712.1
ATP2B4	NM_001365784.2 linkuse as main transcript	c.5C>T	p.Thr2Met	missense_variant	2/21		NP_001352713.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP2B4	ENST00000357681.10 linkuse as main transcript	c.5C>T	p.Thr2Met	missense_variant	2/21	1	NM_001684.5	ENSP00000350310	A1	P23634-6
ATP2B4	ENST00000341360.7 linkuse as main transcript	c.5C>T	p.Thr2Met	missense_variant	2/22	1		ENSP00000340930	P4	P23634-2
ATP2B4	ENST00000705901.1 linkuse as main transcript	c.5C>T	p.Thr2Met	missense_variant	2/21			ENSP00000516177		P23634-3

Frequencies

GnomAD3 genomes

AF:

0.000506

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000916

Gnomad ASJ

AF:

0.0150

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000971

AC:

243

AN:

250326

Hom.:

AF XY:

0.000850

AC XY:

115

AN XY:

135234

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00140

Gnomad ASJ exome

AF:

0.0166

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000133

Gnomad OTH exome

AF:

0.00197

GnomAD4 exome

AF:

0.000470

AC:

686

AN:

1460786

Hom.:

Cov.:

AF XY:

0.000454

AC XY:

330

AN XY:

726608

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00134

Gnomad4 ASJ exome

AF:

0.0173

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000801

Gnomad4 OTH exome

AF:

0.00138

GnomAD4 genome

AF:

0.000506

AC:

AN:

152284

Hom.:

Cov.:

AF XY:

0.000484

AC XY:

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000915

Gnomad4 ASJ

AF:

0.0150

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00110

Hom.:

Bravo

AF:

0.000612

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.000684

AC:

EpiCase

AF:

0.000491

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

ATP2B4-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 15, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 11, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Uncertain

-0.050

CADD

Uncertain

DANN

Pathogenic

1.0

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.70

T;T;.

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.010

T;T;T

MetaSVM

Uncertain

0.73

MutationAssessor

Benign

1.5

L;L;L

MutationTaster

Benign

0.86

D;D;D;D;D

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.95

N;N;N

REVEL

Benign

0.27

Sift

Uncertain

0.0010

D;D;D

Sift4G

Uncertain

0.0050

D;D;D

Polyphen

0.99

D;.;.

Vest4

0.14

MVP

0.53

MPC

1.3

ClinPred

0.064

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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