rs12817819

Variant names:

• chr12-89645549-C-T
• rs12817819
• NM_001366521.1:c.209-3194G>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.209-3194G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0939 in 152,166 control chromosomes in the GnomAD database, including 845 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 0.094 (845 hom., cov: 32)
• Consequence: ATP2B1 NM_001366521.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.883
• Publications: 13 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP2B1	NM_001366521.1	c.209-3194G>A		intron_variant	Intron 2 of 20	ENST00000428670.8	NP_001353450.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP2B1	ENST00000428670.8	c.209-3194G>A		intron_variant	Intron 2 of 20	5	NM_001366521.1	ENSP00000392043.3

Frequencies

GnomAD3 genomes AF: 0.0941 AC: 14303 AN: 152048 Hom.: 845 Cov.: 32

Gnomad AFR AF: 0.0281

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.0855

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.0430

Gnomad SAS AF: 0.0827

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.0976

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

GnomAD4 genome AF: 0.0939 AC: 14292 AN: 152166 Hom.: 845 Cov.: 32 AF XY: 0.0955 AC XY: 7101 AN XY: 74394

African (AFR) AF: 0.0280 AC: 1164 AN: 41550

American (AMR) AF: 0.0854 AC: 1305 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 446 AN: 3472

East Asian (EAS) AF: 0.0431 AC: 223 AN: 5172

South Asian (SAS) AF: 0.0820 AC: 395 AN: 4818

European-Finnish (FIN) AF: 0.156 AC: 1650 AN: 10578

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.128 AC: 8694 AN: 67980

Other (OTH) AF: 0.0961 AC: 203 AN: 2112

Alfa AF: 0.107 Hom.: 2104

Bravo AF: 0.0842

Asia WGS AF: 0.0850 AC: 297 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.0
DANN	Benign	0.58
PhyloP100		0.88
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: rs12817819; hg19: chr12-90039326;