12-89595822-G-A

Variant names:

• chr12-89595822-G-A
• rs1401982
• NM_001366521.1:c.3351+3295C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 23 publications found

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 Gene-Disease associations (from GenCC):

• intellectual developmental disorder, autosomal dominant 66

  Inheritance: AR, AD Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366521.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP2B1	NM_001366521.1	MANE Select	c.3351+3295C>T		intron	N/A	NP_001353450.1
	ATP2B1	NM_001366524.1		c.3438+2835C>T		intron	N/A	NP_001353453.1
	ATP2B1	NM_001366525.1		c.3438+2835C>T		intron	N/A	NP_001353454.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP2B1	ENST00000428670.8	TSL:5 MANE Select	c.3351+3295C>T		intron	N/A	ENSP00000392043.3
	ATP2B1	ENST00000550716.1	TSL:1	c.291+3295C>T		intron	N/A	ENSP00000447096.1
	ATP2B1	ENST00000359142.8	TSL:5	c.3505+2768C>T		intron	N/A	ENSP00000352054.3

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

African (AFR) AF: 0.525 AC: 21740 AN: 41392

American (AMR) AF: 0.699 AC: 10637 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.542 AC: 1878 AN: 3466

East Asian (EAS) AF: 0.636 AC: 3289 AN: 5168

South Asian (SAS) AF: 0.526 AC: 2530 AN: 4806

European-Finnish (FIN) AF: 0.720 AC: 7590 AN: 10542

Middle Eastern (MID) AF: 0.551 AC: 161 AN: 292

European-Non Finnish (NFE) AF: 0.599 AC: 40693 AN: 67900

Other (OTH) AF: 0.600 AC: 1262 AN: 2102

Alfa AF: 0.581 Hom.: 15939

Bravo AF: 0.592

Asia WGS AF: 0.640 AC: 2223 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.66
PhyloP100		-0.19
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1401982; hg19: chr12-89989599;