12-89675499-T-G

Variant names:

• chr12-89675499-T-G
• rs11105364
• NM_001366521.1:c.-221-19392A>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001366521.1(ATP2B1):​c.-221-19392A>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 152,204 control chromosomes in the GnomAD database, including 2,092 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 (2092 hom., cov: 32)
• Consequence: ATP2B1 NM_001366521.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43

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]

ACMG classification

Verdict is Benign. Variant got -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 = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP2B1	NM_001366521.1	c.-221-19392A>C		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.-221-19392A>C		intron_variant	Intron 1 of 20	5	NM_001366521.1	ENSP00000392043.3
ATP2B1	ENST00000359142.8	c.-221-19392A>C		intron_variant	Intron 1 of 21	5		ENSP00000352054.3
ATP2B1	ENST00000551310.2	c.-221-19392A>C		intron_variant	Intron 1 of 21	3		ENSP00000447041.2
ATP2B1	ENST00000705822.1	c.-221-19392A>C		intron_variant	Intron 1 of 21			ENSP00000516172.1

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22899 AN: 152086 Hom.: 2086 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.0648

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.0773

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: 22904 AN: 152204 Hom.: 2092 Cov.: 32 AF XY: 0.152 AC XY: 11343 AN XY: 74450

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.123

Gnomad4 ASJ AF: 0.238

Gnomad4 EAS AF: 0.329

Gnomad4 SAS AF: 0.357

Gnomad4 FIN AF: 0.0773

Gnomad4 NFE AF: 0.164

Gnomad4 OTH AF: 0.162

Alfa AF: 0.156 Hom.: 291

Bravo AF: 0.149

Asia WGS AF: 0.260 AC: 907 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	12
DANN	Benign	0.40

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11105364; hg19: chr12-90069276;