dbSNP rs970: ATP2B4:n.*4177T>C (chr1-203743868-T-C) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4BA1

The ENST00000484746.1(ATP2B4):n.*4177T>C variant causes a non coding transcript exon change. The variant allele was found at a frequency of 0.226 in 152,436 control chromosomes in the GnomAD database, including 4,278 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.23 ( 4277 hom., cov: 32)

Exomes 𝑓: 0.11 ( 1 hom. )

Consequence

ATP2B4
ENST00000484746.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.40

Publications

13 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:

ENSG00000294708 (HGNC:):

ENSG00000294708 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.17).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
ATP2B4	NM_001684.5 link	c.*4014T>C	3_prime_UTR_variant	Exon 21 of 21	ENST00000357681.10	NP_001675.3
ATP2B4	NM_001001396.3 link	c.*4297T>C	3_prime_UTR_variant	Exon 22 of 22		NP_001001396.1
LOC102723543	XR_426890.4 link	n.355+337A>G	intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
ATP2B4	ENST00000484746.1 link	n.*4177T>C	non_coding_transcript_exon_variant	Exon 4 of 4	1		ENSP00000433577.1
ATP2B4	ENST00000357681.10 link	c.*4014T>C	3_prime_UTR_variant	Exon 21 of 21	1	NM_001684.5	ENSP00000350310.5
ATP2B4	ENST00000484746.1 link	n.*4177T>C	3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000433577.1

Frequencies

GnomAD3 genomes

AF:

0.227

AC:

34439

AN:

152016

Hom.:

4279

Cov.:

show subpopulations

Gnomad AFR

AF:

0.232

Gnomad AMI

AF:

0.430

Gnomad AMR

AF:

0.383

Gnomad ASJ

AF:

0.298

Gnomad EAS

AF:

0.186

Gnomad SAS

AF:

0.195

Gnomad FIN

AF:

0.0989

Gnomad MID

AF:

0.342

Gnomad NFE

AF:

0.205

Gnomad OTH

AF:

0.268

GnomAD4 exome

AF:

0.109

AC:

AN:

302

Hom.:

Cov.:

AF XY:

0.144

AC XY:

AN XY:

188

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.108

AC:

AN:

296

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.226

AC:

34456

AN:

152134

Hom.:

4277

Cov.:

AF XY:

0.223

AC XY:

16575

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.232

AC:

9602

AN:

41476

American (AMR)

AF:

0.383

AC:

5845

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.298

AC:

1033

AN:

3472

East Asian (EAS)

AF:

0.186

AC:

965

AN:

5180

South Asian (SAS)

AF:

0.195

AC:

939

AN:

4816

European-Finnish (FIN)

AF:

0.0989

AC:

1050

AN:

10618

Middle Eastern (MID)

AF:

0.344

AC:

101

AN:

294

European-Non Finnish (NFE)

AF:

0.205

AC:

13966

AN:

67984

Other (OTH)

AF:

0.267

AC:

563

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1363

2726

4089

5452

6815

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

360

720

1080

1440

1800

<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:

0.213

Hom.:

4312

Bravo

AF:

0.252

Asia WGS

AF:

0.221

AC:

769

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.17

CADD

Benign

(source)

DANN

Benign

0.91

PhyloP100

5.4

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over