rs12818945

Positions:

• chr12-89624457-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001366521.1(ATP2B1):​c.1130-60G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0531 in 1,359,474 control chromosomes in the GnomAD database, including 2,313 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 0.045 (253 hom., cov: 32)
  • Exomes 𝑓: 0.054 (2060 hom.)
• Consequence: ATP2B1 NM_001366521.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.151

Genes affected

ATP2B1 (HGNC:814): (ATPase plasma membrane Ca2+ transporting 1) 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 1. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ATP2B1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0875 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP2B1	NM_001366521.1	c.1130-60G>T		intron_variant		ENST00000428670.8	NP_001353450.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP2B1	ENST00000428670.8	c.1130-60G>T		intron_variant		5	NM_001366521.1	ENSP00000392043.3
ATP2B1	ENST00000359142.8	c.1130-60G>T		intron_variant		5		ENSP00000352054.3
ATP2B1	ENST00000551310.2	c.1130-60G>T		intron_variant		3		ENSP00000447041.2
ATP2B1	ENST00000705822.1	c.1130-60G>T		intron_variant				ENSP00000516172.1

Frequencies

GnomAD3 genomes AF: 0.0454 AC: 6906 AN: 152100 Hom.: 250 Cov.: 32

Gnomad AFR AF: 0.0110

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0536

Gnomad ASJ AF: 0.00576

Gnomad EAS AF: 0.0942

Gnomad SAS AF: 0.0532

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0527

Gnomad OTH AF: 0.0358

GnomAD4 exome AF: 0.0541 AC: 65259 AN: 1207256 Hom.: 2060 AF XY: 0.0535 AC XY: 32377 AN XY: 605008

Gnomad4 AFR exome AF: 0.00786

Gnomad4 AMR exome AF: 0.0698

Gnomad4 ASJ exome AF: 0.00408

Gnomad4 EAS exome AF: 0.100

Gnomad4 SAS exome AF: 0.0481

Gnomad4 FIN exome AF: 0.100

Gnomad4 NFE exome AF: 0.0527

Gnomad4 OTH exome AF: 0.0475

GnomAD4 genome AF: 0.0454 AC: 6916 AN: 152218 Hom.: 253 Cov.: 32 AF XY: 0.0483 AC XY: 3592 AN XY: 74424

Gnomad4 AFR AF: 0.0110

Gnomad4 AMR AF: 0.0541

Gnomad4 ASJ AF: 0.00576

Gnomad4 EAS AF: 0.0944

Gnomad4 SAS AF: 0.0533

Gnomad4 FIN AF: 0.112

Gnomad4 NFE AF: 0.0527

Gnomad4 OTH AF: 0.0359

Alfa AF: 0.0468 Hom.: 43

Bravo AF: 0.0414

Asia WGS AF: 0.0680 AC: 234 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.1
DANN	Benign	0.51

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: rs12818945; hg19: chr12-90018234;