Variant 12-89591227-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.208

Variant links:

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 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 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_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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP2B1	NM_001366521.1 linkuse as main transcript	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 linkuse as main transcript	c.3420G>T	p.Ser1140=	synonymous_variant	21/21	5	NM_001366521.1	P1	P20020-3
	ENST00000552778.2 linkuse as main transcript	n.148-2088C>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0158

AC:

2397

AN:

151986

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00474

AC XY:

642

AN XY:

135500

show subpopulations

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.:

Cov.:

AF XY:

0.00282

AC XY:

2052

AN XY:

726692

show subpopulations

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.:

Cov.:

AF XY:

0.0151

AC XY:

1125

AN XY:

74380

show subpopulations

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.:

Bravo

AF:

0.0180

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.00164

EpiControl

AF:

0.00207

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 16, 2018	- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over