rs2236552

Variant names:

• chr1-203711292-T-C
• rs2236552
• NM_001684.5:c.2031+184T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001684.5(ATP2B4):​c.2031+184T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0917 in 152,182 control chromosomes in the GnomAD database, including 1,712 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 0.092 (1712 hom., cov: 31)
• Consequence: ATP2B4 NM_001684.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.539
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP2B4	NM_001684.5	c.2031+184T>C		intron_variant	Intron 12 of 20	ENST00000357681.10	NP_001675.3
ATP2B4	NM_001001396.3	c.2031+184T>C		intron_variant	Intron 12 of 21		NP_001001396.1
ATP2B4	NM_001365783.2	c.2031+184T>C		intron_variant	Intron 12 of 20		NP_001352712.1
ATP2B4	NM_001365784.2	c.2031+184T>C		intron_variant	Intron 12 of 20		NP_001352713.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP2B4	ENST00000357681.10	c.2031+184T>C		intron_variant	Intron 12 of 20	1	NM_001684.5	ENSP00000350310.5
ATP2B4	ENST00000341360.7	c.2031+184T>C		intron_variant	Intron 12 of 21	1		ENSP00000340930.2
ATP2B4	ENST00000705901.1	c.1995+184T>C		intron_variant	Intron 11 of 20			ENSP00000516177.1

Frequencies

GnomAD3 genomes AF: 0.0916 AC: 13924 AN: 152064 Hom.: 1710 Cov.: 31

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0356

Gnomad ASJ AF: 0.0124

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.0623

Gnomad FIN AF: 0.0147

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.00459

Gnomad OTH AF: 0.0760

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0917 AC: 13955 AN: 152182 Hom.: 1712 Cov.: 31 AF XY: 0.0917 AC XY: 6824 AN XY: 74428

African (AFR) AF: 0.260 AC: 10801 AN: 41472

American (AMR) AF: 0.0355 AC: 543 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0124 AC: 43 AN: 3470

East Asian (EAS) AF: 0.314 AC: 1626 AN: 5172

South Asian (SAS) AF: 0.0626 AC: 302 AN: 4826

European-Finnish (FIN) AF: 0.0147 AC: 156 AN: 10620

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.00459 AC: 312 AN: 68010

Other (OTH) AF: 0.0762 AC: 161 AN: 2114

Alfa AF: 0.0399 Hom.: 1883

Bravo AF: 0.103

Asia WGS AF: 0.174 AC: 605 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.7
DANN	Benign	0.55
PhyloP100		0.54
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2236552; hg19: chr1-203680420;