12-89591227-C-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_001366521.1(ATP2B1):c.3420G>T(p.Ser1140=) 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, single submitter B:1
• Conservation: PhyloP100: -0.208

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 12-89591227-C-A is Benign according to our data. Variant chr12-89591227-C-A is described in ClinVar as [Benign]. Clinvar id is 784251.Status of the report is criteria_provided_single_submitter, 1 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP2B1	NM_001366521.1	c.3420G>T	p.Ser1140=	synonymous_variant	21/21	ENST00000428670.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP2B1	ENST00000428670.8	c.3420G>T	p.Ser1140=	synonymous_variant	21/21	5	NM_001366521.1	P1
	ENST00000552778.2	n.148-2088C>A		intron_variant, non_coding_transcript_variant		3

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

GnomAD3 exomes AF: 0.00567 AC: 1422 AN: 250684 Hom.: 20 AF XY: 0.00474 AC XY: 642 AN XY: 135500

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 SAS exome AF: 0.00239

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

Gnomad4 AFR exome AF: 0.0534

Gnomad4 AMR exome AF: 0.00566

Gnomad4 ASJ exome AF: 0.0124

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00103

Gnomad4 OTH exome AF: 0.00610

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

Gnomad4 AFR AF: 0.0507

Gnomad4 AMR AF: 0.00794

Gnomad4 ASJ AF: 0.0118

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00132

Gnomad4 OTH AF: 0.0152

Alfa AF: 0.00708 Hom.: 7

Bravo AF: 0.0180

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.00164

EpiControl AF: 0.00207

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 16, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
Cadd	Benign	1.3
Dann	Benign	0.80

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

Publications

LitVar

Other links and lift over

dbSNP: rs61736878; hg19: chr12-89985004;