rs11105378

Variant names:

• chr12-89696964-C-T
• rs11105378
• NM_001366521.1:c.-222+11632G>A

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+11632G>A 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 149,226 control chromosomes in the GnomAD database, including 2,037 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 (2037 hom., cov: 31)
• Consequence: ATP2B1 NM_001366521.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13
• Publications: 24 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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP2B1	NM_001366521.1	c.-222+11632G>A		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+11632G>A		intron_variant	Intron 1 of 20	5	NM_001366521.1	ENSP00000392043.3
ATP2B1	ENST00000359142.8	c.-222+11632G>A		intron_variant	Intron 1 of 21	5		ENSP00000352054.3
ATP2B1	ENST00000551310.2	c.-222+12255G>A		intron_variant	Intron 1 of 21	3		ENSP00000447041.2
ATP2B1	ENST00000705822.1	c.-222+12255G>A		intron_variant	Intron 1 of 21			ENSP00000516172.1

Frequencies

GnomAD3 genomes AF: 0.152 AC: 22660 AN: 149158 Hom.: 2032 Cov.: 31

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.0650

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.0831

Gnomad MID AF: 0.240

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.165

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

GnomAD4 genome AF: 0.152 AC: 22658 AN: 149226 Hom.: 2037 Cov.: 31 AF XY: 0.154 AC XY: 11187 AN XY: 72588

African (AFR) AF: 0.107 AC: 4332 AN: 40542

American (AMR) AF: 0.126 AC: 1878 AN: 14910

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 818 AN: 3464

East Asian (EAS) AF: 0.328 AC: 1668 AN: 5084

South Asian (SAS) AF: 0.346 AC: 1644 AN: 4748

European-Finnish (FIN) AF: 0.0831 AC: 802 AN: 9656

Middle Eastern (MID) AF: 0.248 AC: 71 AN: 286

European-Non Finnish (NFE) AF: 0.164 AC: 11049 AN: 67570

Other (OTH) AF: 0.164 AC: 337 AN: 2058

Alfa AF: 0.139 Hom.: 401

Bravo AF: 0.148

Asia WGS AF: 0.251 AC: 876 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.9
DANN	Benign	0.76
PhyloP100		-1.1
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: rs11105378; hg19: chr12-90090741;