Variant chr12-121641523-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_032790.3(ORAI1):c.789T>C(p.Val263=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0139 in 1,613,696 control chromosomes in the GnomAD database, including 872 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.030 ( 178 hom., cov: 33)

Exomes 𝑓: 0.012 ( 694 hom. )

Consequence

ORAI1
NM_032790.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.14

Variant links:

Genes affected

ORAI1 (HGNC:25896): (ORAI calcium release-activated calcium modulator 1) The protein encoded by this gene is a membrane calcium channel subunit that is activated by the calcium sensor STIM1 when calcium stores are depleted. This type of channel is the primary way for calcium influx into T-cells. Defects in this gene are a cause of immune dysfunction with T-cell inactivation due to calcium entry defect type 1 (IDTICED1). [provided by RefSeq, Sep 2011]

ORAI1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 12-121641523-T-C is Benign according to our data. Variant chr12-121641523-T-C is described in ClinVar as [Benign]. Clinvar id is 379438.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.14 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ORAI1	NM_032790.3 linkuse as main transcript	c.789T>C	p.Val263=	synonymous_variant	3/3		NP_116179.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	Protein	Appris	UniProt
ORAI1	ENST00000617316.2 linkuse as main transcript	c.786T>C	p.Val262=	synonymous_variant	3/3	1	ENSP00000482568	P1	Q96D31-1
ORAI1	ENST00000611718.1 linkuse as main transcript	n.842T>C		non_coding_transcript_exon_variant	2/2	5
ORAI1	ENST00000646827.1 linkuse as main transcript	n.984T>C		non_coding_transcript_exon_variant	2/2
ORAI1	ENST00000698901.1 linkuse as main transcript	n.908T>C		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes

AF:

0.0296

AC:

4506

AN:

152202

Hom.:

177

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0765

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.0122

Gnomad ASJ

AF:

0.00230

Gnomad EAS

AF:

0.112

Gnomad SAS

AF:

0.0103

Gnomad FIN

AF:

0.00499

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00594

Gnomad OTH

AF:

0.0234

GnomAD3 exomes

AF:

0.0166

AC:

4136

AN:

248536

Hom.:

154

AF XY:

0.0148

AC XY:

2003

AN XY:

134994

show subpopulations

Gnomad AFR exome

AF:

0.0779

Gnomad AMR exome

AF:

0.00655

Gnomad ASJ exome

AF:

0.00278

Gnomad EAS exome

AF:

0.0916

Gnomad SAS exome

AF:

0.00624

Gnomad FIN exome

AF:

0.00590

Gnomad NFE exome

AF:

0.00567

Gnomad OTH exome

AF:

0.0124

GnomAD4 exome

AF:

0.0123

AC:

17959

AN:

1461376

Hom.:

694

Cov.:

AF XY:

0.0119

AC XY:

8670

AN XY:

727036

show subpopulations

Gnomad4 AFR exome

AF:

0.0802

Gnomad4 AMR exome

AF:

0.00666

Gnomad4 ASJ exome

AF:

0.00214

Gnomad4 EAS exome

AF:

0.149

Gnomad4 SAS exome

AF:

0.00694

Gnomad4 FIN exome

AF:

0.00557

Gnomad4 NFE exome

AF:

0.00643

Gnomad4 OTH exome

AF:

0.0153

GnomAD4 genome

AF:

0.0296

AC:

4515

AN:

152320

Hom.:

178

Cov.:

AF XY:

0.0297

AC XY:

2210

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.0764

Gnomad4 AMR

AF:

0.0122

Gnomad4 ASJ

AF:

0.00230

Gnomad4 EAS

AF:

0.112

Gnomad4 SAS

AF:

0.0108

Gnomad4 FIN

AF:

0.00499

Gnomad4 NFE

AF:

0.00594

Gnomad4 OTH

AF:

0.0232

Alfa

AF:

0.0136

Hom.:

Bravo

AF:

0.0318

Asia WGS

AF:

0.0580

AC:

202

AN:

3478

EpiCase

AF:

0.00562

EpiControl

AF:

0.00551

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 13, 2016

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Combined immunodeficiency due to ORAI1 deficiency;C4014557:Myopathy, tubular aggregate, 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.65

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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