rs17381194

Variant names:

• chr12-89617318-T-C
• rs17381194
• NM_001366521.1:c.1830-279A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001366521.1(ATP2B1):​c.1830-279A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,202 control chromosomes in the GnomAD database, including 1,128 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 0.10 (1128 hom., cov: 32)
• Consequence: ATP2B1 NM_001366521.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.654
• Publications: 9 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 = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP2B1	NM_001366521.1	c.1830-279A>G		intron_variant	Intron 11 of 20	ENST00000428670.8	NP_001353450.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP2B1	ENST00000428670.8	c.1830-279A>G		intron_variant	Intron 11 of 20	5	NM_001366521.1	ENSP00000392043.3
ATP2B1	ENST00000359142.8	c.1830-279A>G		intron_variant	Intron 11 of 21	5		ENSP00000352054.3
ATP2B1	ENST00000551310.2	c.1830-279A>G		intron_variant	Intron 11 of 21	3		ENSP00000447041.2
ATP2B1	ENST00000705822.1	c.1830-279A>G		intron_variant	Intron 11 of 21			ENSP00000516172.1

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15821 AN: 152084 Hom.: 1128 Cov.: 32

Gnomad AFR AF: 0.0247

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.0887

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0553

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.110

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

GnomAD4 genome AF: 0.104 AC: 15816 AN: 152202 Hom.: 1128 Cov.: 32 AF XY: 0.103 AC XY: 7636 AN XY: 74408

African (AFR) AF: 0.0246 AC: 1024 AN: 41560

American (AMR) AF: 0.0886 AC: 1355 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 434 AN: 3468

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5184

South Asian (SAS) AF: 0.0551 AC: 266 AN: 4828

European-Finnish (FIN) AF: 0.156 AC: 1653 AN: 10588

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.155 AC: 10528 AN: 67966

Other (OTH) AF: 0.109 AC: 231 AN: 2114

Alfa AF: 0.134 Hom.: 2869

Bravo AF: 0.0975

Asia WGS AF: 0.0250 AC: 89 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.5
DANN	Benign	0.83
PhyloP100		-0.65
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: rs17381194; hg19: chr12-90011095;