rs17381194

Positions:

• chr12-89617318-T-C

Variant summary

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

The NM_001366521.1(ATP2B1):​c.1830-279A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,202 control chromosomes in the GnomAD database, including 1,128 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 0.10 (1128 hom., cov: 32)
• Consequence: ATP2B1 NM_001366521.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.654

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP2B1	NM_001366521.1	c.1830-279A>G		intron_variant		ENST00000428670.8	NP_001353450.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP2B1	ENST00000428670.8	c.1830-279A>G		intron_variant		5	NM_001366521.1	ENSP00000392043	P1
ATP2B1	ENST00000359142.8	c.1830-279A>G		intron_variant		5		ENSP00000352054
ATP2B1	ENST00000551310.2	c.1830-279A>G		intron_variant		3		ENSP00000447041
ATP2B1	ENST00000705822.1	c.1830-279A>G		intron_variant				ENSP00000516172

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15821 AN: 152084 Hom.: 1128 Cov.: 32

Gnomad AFR AF: 0.0247

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.0887

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0553

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.110

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

GnomAD4 genome AF: 0.104 AC: 15816 AN: 152202 Hom.: 1128 Cov.: 32 AF XY: 0.103 AC XY: 7636 AN XY: 74408

Gnomad4 AFR AF: 0.0246

Gnomad4 AMR AF: 0.0886

Gnomad4 ASJ AF: 0.125

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0551

Gnomad4 FIN AF: 0.156

Gnomad4 NFE AF: 0.155

Gnomad4 OTH AF: 0.109

Alfa AF: 0.137 Hom.: 772

Bravo AF: 0.0975

Asia WGS AF: 0.0250 AC: 89 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.5
DANN	Benign	0.83

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: rs17381194; hg19: chr12-90011095;