rs1401982

Positions:

• chr12-89595822-G-A
• chr12-89595822-G-T

Variant summary

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

The NM_001366521.1(ATP2B1):​c.3351+3295C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.595 in 151,808 control chromosomes in the GnomAD database, including 27,377 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 0.59 (27377 hom., cov: 31)
• Consequence: ATP2B1 NM_001366521.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.193

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP2B1	NM_001366521.1	c.3351+3295C>T		intron_variant		ENST00000428670.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP2B1	ENST00000428670.8	c.3351+3295C>T		intron_variant		5	NM_001366521.1	P1

Frequencies

GnomAD3 genomes AF: 0.595 AC: 90256 AN: 151686 Hom.: 27346 Cov.: 31

Gnomad AFR AF: 0.526

Gnomad AMI AF: 0.588

Gnomad AMR AF: 0.698

Gnomad ASJ AF: 0.542

Gnomad EAS AF: 0.636

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.720

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.599

Gnomad OTH AF: 0.598

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

GnomAD4 genome AF: 0.595 AC: 90316 AN: 151808 Hom.: 27377 Cov.: 31 AF XY: 0.599 AC XY: 44454 AN XY: 74182

Gnomad4 AFR AF: 0.525

Gnomad4 AMR AF: 0.699

Gnomad4 ASJ AF: 0.542

Gnomad4 EAS AF: 0.636

Gnomad4 SAS AF: 0.526

Gnomad4 FIN AF: 0.720

Gnomad4 NFE AF: 0.599

Gnomad4 OTH AF: 0.600

Alfa AF: 0.588 Hom.: 12294

Bravo AF: 0.592

Asia WGS AF: 0.640 AC: 2223 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.66

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: rs1401982; hg19: chr12-89989599;