rs11105354

Variant names:

• chr12-89632746-A-G
• rs11105354
• NM_001366521.1:c.787+2032T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001366521.1(ATP2B1):​c.787+2032T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 152,226 control chromosomes in the GnomAD database, including 2,086 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 (2086 hom., cov: 32)
• Consequence: ATP2B1 NM_001366521.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.44
• Publications: 31 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP2B1	NM_001366521.1	c.787+2032T>C		intron_variant	Intron 5 of 20	ENST00000428670.8	NP_001353450.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP2B1	ENST00000428670.8	c.787+2032T>C		intron_variant	Intron 5 of 20	5	NM_001366521.1	ENSP00000392043.3

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22883 AN: 152108 Hom.: 2081 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.0772

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.163

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

GnomAD4 genome AF: 0.150 AC: 22888 AN: 152226 Hom.: 2086 Cov.: 32 AF XY: 0.152 AC XY: 11319 AN XY: 74440

African (AFR) AF: 0.105 AC: 4344 AN: 41548

American (AMR) AF: 0.123 AC: 1886 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 835 AN: 3470

East Asian (EAS) AF: 0.330 AC: 1707 AN: 5178

South Asian (SAS) AF: 0.353 AC: 1701 AN: 4824

European-Finnish (FIN) AF: 0.0772 AC: 819 AN: 10610

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.164 AC: 11119 AN: 67998

Other (OTH) AF: 0.163 AC: 344 AN: 2114

Alfa AF: 0.140 Hom.: 623

Bravo AF: 0.149

Asia WGS AF: 0.255 AC: 892 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	17
DANN	Benign	0.83
PhyloP100		1.4
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: rs11105354; hg19: chr12-90026523;