12-89591227-C-A

Variant names:

• chr12-89591227-C-A
• rs61736878
• NM_001366521.1:c.3420G>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001366521.1(ATP2B1):​c.3420G>T​(p.Ser1140Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00407 in 1,612,972 control chromosomes in the GnomAD database, including 114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (49 hom., cov: 32)
  • Exomes 𝑓: 0.0028 (65 hom.)
• Consequence: ATP2B1 NM_001366521.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.208
• Publications: 2 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]

POC1B-AS1 (HGNC:52949): (POC1B antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.138).
• BP6: Variant 12-89591227-C-A is Benign according to our data. Variant chr12-89591227-C-A is described in ClinVar as Benign. ClinVar VariationId is 784251.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.208 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0514 is higher than 0.05.

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.3420G>T	p.Ser1140Ser	synonymous	Exon 21 of 21	NP_001353450.1	P20020-3
	ATP2B1	NM_001366524.1		c.3507G>T	p.Ser1169Ser	synonymous	Exon 22 of 22	NP_001353453.1	P20020-4
	ATP2B1	NM_001366525.1		c.3507G>T	p.Ser1169Ser	synonymous	Exon 22 of 22	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.3420G>T	p.Ser1140Ser	synonymous	Exon 21 of 21	ENSP00000392043.3	P20020-3
	ATP2B1	ENST00000550716.1	TSL:1	c.360G>T	p.Ser120Ser	synonymous	Exon 3 of 3	ENSP00000447096.1	H0YHH6
	ATP2B1	ENST00000960959.1		c.3534G>T	p.Ser1178Ser	synonymous	Exon 22 of 22	ENSP00000631018.1

Frequencies

GnomAD3 genomes AF: 0.0158 AC: 2397 AN: 151986 Hom.: 48 Cov.: 32

Gnomad AFR AF: 0.0505

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00795

Gnomad ASJ AF: 0.0118

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.00134

Gnomad OTH AF: 0.0153

GnomAD2 exomes AF: 0.00567 AC: 1422 AN: 250684 AF XY: 0.00474

Gnomad AFR exome AF: 0.0508

Gnomad AMR exome AF: 0.00528

Gnomad ASJ exome AF: 0.0130

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00155

Gnomad OTH exome AF: 0.00574

GnomAD4 exome AF: 0.00285 AC: 4158 AN: 1460868 Hom.: 65 Cov.: 31 AF XY: 0.00282 AC XY: 2052 AN XY: 726692

African (AFR) AF: 0.0534 AC: 1787 AN: 33436

American (AMR) AF: 0.00566 AC: 253 AN: 44670

Ashkenazi Jewish (ASJ) AF: 0.0124 AC: 324 AN: 26090

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.00232 AC: 200 AN: 86204

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53354

Middle Eastern (MID) AF: 0.0134 AC: 77 AN: 5758

European-Non Finnish (NFE) AF: 0.00103 AC: 1149 AN: 1111326

Other (OTH) AF: 0.00610 AC: 368 AN: 60352

GnomAD4 genome AF: 0.0158 AC: 2408 AN: 152104 Hom.: 49 Cov.: 32 AF XY: 0.0151 AC XY: 1125 AN XY: 74380

African (AFR) AF: 0.0507 AC: 2103 AN: 41518

American (AMR) AF: 0.00794 AC: 121 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.0118 AC: 41 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.00132 AC: 90 AN: 67946

Other (OTH) AF: 0.0152 AC: 32 AN: 2112

Alfa AF: 0.00743 Hom.: 15

Bravo AF: 0.0180

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.00164

EpiControl AF: 0.00207

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	1.3
DANN	Benign	0.80
PhyloP100		-0.21
Mutation Taster		=96/4	polymorphism

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: rs61736878; hg19: chr12-89985004;