rs12230074

Variant names:

• chr12-89697090-A-G
• rs12230074
• NM_001366521.1:c.-222+11506T>C

Your query was ambiguous. Multiple possible variants found:

• chr12-89697090-A-G
• chr12-89697090-A-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.-222+11506T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 148,298 control chromosomes in the GnomAD database, including 2,077 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 0.15 (2077 hom., cov: 29)
• Consequence: ATP2B1 NM_001366521.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.108
• Publications: 12 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 (SAS) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP2B1	NM_001366521.1	c.-222+11506T>C		intron_variant	Intron 1 of 20	ENST00000428670.8	NP_001353450.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP2B1	ENST00000428670.8	c.-222+11506T>C		intron_variant	Intron 1 of 20	5	NM_001366521.1	ENSP00000392043.3
ATP2B1	ENST00000359142.8	c.-222+11506T>C		intron_variant	Intron 1 of 21	5		ENSP00000352054.3
ATP2B1	ENST00000551310.2	c.-222+12129T>C		intron_variant	Intron 1 of 21	3		ENSP00000447041.2
ATP2B1	ENST00000705822.1	c.-222+12129T>C		intron_variant	Intron 1 of 21			ENSP00000516172.1

Frequencies

GnomAD3 genomes AF: 0.152 AC: 22550 AN: 148236 Hom.: 2072 Cov.: 29

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.0651

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.0706

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.164

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

GnomAD4 genome AF: 0.152 AC: 22545 AN: 148298 Hom.: 2077 Cov.: 29 AF XY: 0.153 AC XY: 11044 AN XY: 72148

African (AFR) AF: 0.113 AC: 4590 AN: 40510

American (AMR) AF: 0.124 AC: 1847 AN: 14882

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 816 AN: 3446

East Asian (EAS) AF: 0.326 AC: 1635 AN: 5014

South Asian (SAS) AF: 0.344 AC: 1612 AN: 4684

European-Finnish (FIN) AF: 0.0706 AC: 657 AN: 9308

Middle Eastern (MID) AF: 0.239 AC: 67 AN: 280

European-Non Finnish (NFE) AF: 0.163 AC: 10928 AN: 67210

Other (OTH) AF: 0.162 AC: 334 AN: 2058

Alfa AF: 0.146 Hom.: 789

Bravo AF: 0.152

Asia WGS AF: 0.247 AC: 861 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.5
DANN	Benign	0.65
PhyloP100		0.11
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs12230074; hg19: chr12-90090867;