rs2236552

chr1-203711292-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
ATP2B4	NM_001684.5	c.2031+184T>C		intron_variant		ENST00000357681.10
ATP2B4	NM_001001396.3	c.2031+184T>C		intron_variant
ATP2B4	NM_001365783.2	c.2031+184T>C		intron_variant
ATP2B4	NM_001365784.2	c.2031+184T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP2B4	ENST00000357681.10	c.2031+184T>C		intron_variant		1	NM_001684.5	A1
ATP2B4	ENST00000341360.7	c.2031+184T>C		intron_variant		1		P4
ATP2B4	ENST00000705901.1	c.1995+184T>C		intron_variant

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

Gnomad4 AFR AF: 0.260

Gnomad4 AMR AF: 0.0355

Gnomad4 ASJ AF: 0.0124

Gnomad4 EAS AF: 0.314

Gnomad4 SAS AF: 0.0626

Gnomad4 FIN AF: 0.0147

Gnomad4 NFE AF: 0.00459

Gnomad4 OTH AF: 0.0762

Alfa AF: 0.0198 Hom.: 489

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

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

LitVar

Other links and lift over

dbSNP: rs2236552; hg19: chr1-203680420;