1-203683316-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001684.5(ATP2B4):c.111A>G(p.Ser37Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.886 in 1,614,012 control chromosomes in the GnomAD database, including 635,665 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.83 ( 53556 hom., cov: 32)

Exomes 𝑓: 0.89 ( 582109 hom. )

Consequence

ATP2B4
NM_001684.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.54

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 1-203683316-A-G is Benign according to our data. Variant chr1-203683316-A-G is described in ClinVar as [Benign]. Clinvar id is 1598820.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.54 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP2B4	NM_001684.5 link	c.111A>G	p.Ser37Ser	synonymous_variant	Exon 2 of 21	ENST00000357681.10	NP_001675.3	P23634-6A0A024R968
ATP2B4	NM_001001396.3 link	c.111A>G	p.Ser37Ser	synonymous_variant	Exon 2 of 22		NP_001001396.1	P23634-2
ATP2B4	NM_001365783.2 link	c.111A>G	p.Ser37Ser	synonymous_variant	Exon 2 of 21		NP_001352712.1
ATP2B4	NM_001365784.2 link	c.111A>G	p.Ser37Ser	synonymous_variant	Exon 2 of 21		NP_001352713.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ATP2B4	ENST00000357681.10 link	c.111A>G	p.Ser37Ser	synonymous_variant	Exon 2 of 21	1	NM_001684.5	ENSP00000350310.5	P23634-6
ATP2B4	ENST00000341360.7 link	c.111A>G	p.Ser37Ser	synonymous_variant	Exon 2 of 22	1		ENSP00000340930.2	P23634-2
ATP2B4	ENST00000705901.1 link	c.111A>G	p.Ser37Ser	synonymous_variant	Exon 2 of 21			ENSP00000516177.1	P23634-3

Frequencies

GnomAD3 genomes

AF:

0.833

AC:

126625

AN:

152042

Hom.:

53548

Cov.:

show subpopulations

Gnomad AFR

AF:

0.682

Gnomad AMI

AF:

0.939

Gnomad AMR

AF:

0.902

Gnomad ASJ

AF:

0.908

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.855

Gnomad FIN

AF:

0.822

Gnomad MID

AF:

0.918

Gnomad NFE

AF:

0.890

Gnomad OTH

AF:

0.859

GnomAD2 exomes

AF:

0.883

AC:

221989

AN:

251452

AF XY:

0.883

show subpopulations

Gnomad AFR exome

AF:

0.674

Gnomad AMR exome

AF:

0.944

Gnomad ASJ exome

AF:

0.900

Gnomad EAS exome

AF:

0.999

Gnomad FIN exome

AF:

0.829

Gnomad NFE exome

AF:

0.889

Gnomad OTH exome

AF:

0.891

GnomAD4 exome

AF:

0.891

AC:

1302603

AN:

1461852

Hom.:

582109

Cov.:

AF XY:

0.890

AC XY:

647305

AN XY:

727226

show subpopulations

African (AFR)

AF:

0.665

AC:

22263

AN:

33478

American (AMR)

AF:

0.940

AC:

42054

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.900

AC:

23519

AN:

26134

East Asian (EAS)

AF:

1.00

AC:

39690

AN:

39700

South Asian (SAS)

AF:

0.858

AC:

74038

AN:

86252

European-Finnish (FIN)

AF:

0.830

AC:

44318

AN:

53418

Middle Eastern (MID)

AF:

0.891

AC:

5137

AN:

5768

European-Non Finnish (NFE)

AF:

0.897

AC:

997832

AN:

1111984

Other (OTH)

AF:

0.890

AC:

53752

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

8149

16298

24448

32597

40746

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.832

AC:

126668

AN:

152160

Hom.:

53556

Cov.:

AF XY:

0.831

AC XY:

61846

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.681

AC:

28231

AN:

41470

American (AMR)

AF:

0.902

AC:

13795

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.908

AC:

3150

AN:

3470

East Asian (EAS)

AF:

0.999

AC:

5172

AN:

5176

South Asian (SAS)

AF:

0.854

AC:

4123

AN:

4826

European-Finnish (FIN)

AF:

0.822

AC:

8711

AN:

10598

Middle Eastern (MID)

AF:

0.915

AC:

269

AN:

294

European-Non Finnish (NFE)

AF:

0.890

AC:

60542

AN:

68014

Other (OTH)

AF:

0.860

AC:

1819

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1027

2054

3082

4109

5136

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.878

Hom.:

128617

Bravo

AF:

0.835

Asia WGS

AF:

0.926

AC:

3221

AN:

3478

EpiCase

AF:

0.894

EpiControl

AF:

0.889

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.054

(source)

DANN

Benign

0.34

PhyloP100

-3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(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

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1-203683316-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over