rs17249754

Positions:

• chr12-89666809-G-A

Variant summary

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

The NM_001366521.1(ATP2B1):​c.-221-10702C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 151,846 control chromosomes in the GnomAD database, including 2,182 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 0.16 (2182 hom., cov: 31)
• Consequence: ATP2B1 NM_001366521.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.182

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP2B1	NM_001366521.1	c.-221-10702C>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.-221-10702C>T		intron_variant		5	NM_001366521.1	ENSP00000392043	P1
ATP2B1	ENST00000359142.8	c.-221-10702C>T		intron_variant		5		ENSP00000352054
ATP2B1	ENST00000551310.2	c.-221-10702C>T		intron_variant		3		ENSP00000447041
ATP2B1	ENST00000705822.1	c.-221-10702C>T		intron_variant				ENSP00000516172

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23653 AN: 151728 Hom.: 2175 Cov.: 31

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.0648

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.0776

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.168

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

GnomAD4 genome AF: 0.156 AC: 23663 AN: 151846 Hom.: 2182 Cov.: 31 AF XY: 0.157 AC XY: 11676 AN XY: 74222

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.126

Gnomad4 ASJ AF: 0.238

Gnomad4 EAS AF: 0.328

Gnomad4 SAS AF: 0.358

Gnomad4 FIN AF: 0.0776

Gnomad4 NFE AF: 0.164

Gnomad4 OTH AF: 0.167

Alfa AF: 0.176 Hom.: 3158

Bravo AF: 0.155

Asia WGS AF: 0.261 AC: 911 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.3
DANN	Benign	0.66

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs17249754; hg19: chr12-90060586;