chr1-203683224-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001684.5(ATP2B4):c.19C>T(p.Arg7Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000195 in 1,613,910 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R7H) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00099 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

ATP2B4
NM_001684.5 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.93

Publications

4 publications found

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 was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0044196546).

BP6

Variant 1-203683224-C-T is Benign according to our data. Variant chr1-203683224-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 703903.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 150 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001684.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATP2B4	NM_001684.5	MANE Select	c.19C>T	p.Arg7Cys	missense	Exon 2 of 21	NP_001675.3
ATP2B4	NM_001001396.3		c.19C>T	p.Arg7Cys	missense	Exon 2 of 22	NP_001001396.1	P23634-2
ATP2B4	NM_001365783.2		c.19C>T	p.Arg7Cys	missense	Exon 2 of 21	NP_001352712.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATP2B4	ENST00000357681.10	TSL:1 MANE Select	c.19C>T	p.Arg7Cys	missense	Exon 2 of 21	ENSP00000350310.5	P23634-6
ATP2B4	ENST00000341360.7	TSL:1	c.19C>T	p.Arg7Cys	missense	Exon 2 of 22	ENSP00000340930.2	P23634-2
ATP2B4	ENST00000890814.1		c.19C>T	p.Arg7Cys	missense	Exon 2 of 21	ENSP00000560873.1

Frequencies

GnomAD3 genomes

AF:

0.000960

AC:

146

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00331

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000523

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000319

AC:

AN:

251060

AF XY:

0.000273

show subpopulations

Gnomad AFR exome

AF:

0.00375

Gnomad AMR exome

AF:

0.000348

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000112

AC:

164

AN:

1461648

Hom.:

Cov.:

AF XY:

0.000102

AC XY:

AN XY:

727134

show subpopulations

African (AFR)

AF:

0.00335

AC:

112

AN:

33472

American (AMR)

AF:

0.000224

AC:

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.0000464

AC:

AN:

86212

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.000870

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

0.0000135

AC:

AN:

1111882

Other (OTH)

AF:

0.000298

AC:

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000985

AC:

150

AN:

152262

Hom.:

Cov.:

AF XY:

0.00105

AC XY:

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.00339

AC:

141

AN:

41542

American (AMR)

AF:

0.000523

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68020

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00000873

Hom.:

Bravo

AF:

0.00109

ESP6500AA

AF:

0.00363

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000420

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

(source)

DANN

Uncertain

1.0

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.41

LIST_S2

Uncertain

0.92

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.0044

MetaSVM

Uncertain

-0.035

MutationAssessor

Benign

0.34

PhyloP100

2.9

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.74

REVEL

Uncertain

0.29

Sift

Benign

0.19

Sift4G

Benign

0.19

Polyphen

0.90

Vest4

0.14

MVP

0.47

MPC

1.2

ClinPred

0.017

GERP RS

5.1

PromoterAI

-0.0076

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.37

Mutation Taster

=95/5

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over