chr12-89624457-C-T

Variant names:

• chr12-89624457-C-T
• rs12818945
• NM_001366521.1:c.1130-60G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001366521.1(ATP2B1):​c.1130-60G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000828 in 1,207,782 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 8.3e-7 (0 hom.)
• Consequence: ATP2B1 NM_001366521.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.151
• Publications: 0 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: AD, AR Classification: STRONG, MODERATE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366521.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP2B1	NM_001366521.1	MANE Select	c.1130-60G>A		intron	N/A	NP_001353450.1	P20020-3
	ATP2B1	NM_001366524.1		c.1130-60G>A		intron	N/A	NP_001353453.1	P20020-4
	ATP2B1	NM_001366525.1		c.1130-60G>A		intron	N/A	NP_001353454.1	P20020-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP2B1	ENST00000428670.8	TSL:5 MANE Select	c.1130-60G>A		intron	N/A	ENSP00000392043.3	P20020-3
	ATP2B1	ENST00000960959.1		c.1130-60G>A		intron	N/A	ENSP00000631018.1
	ATP2B1	ENST00000960960.1		c.1130-60G>A		intron	N/A	ENSP00000631019.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.28e-7 AC: 1 AN: 1207782 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 605254

African (AFR) AF: 0.00 AC: 0 AN: 26850

American (AMR) AF: 0.00 AC: 0 AN: 35044

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21822

East Asian (EAS) AF: 0.00 AC: 0 AN: 36946

South Asian (SAS) AF: 0.00 AC: 0 AN: 70396

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3794

European-Non Finnish (NFE) AF: 0.00000109 AC: 1 AN: 914024

Other (OTH) AF: 0.00 AC: 0 AN: 51316

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.6
DANN	Benign	0.51
PhyloP100		-0.15

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: rs12818945; hg19: chr12-90018234;