ENST00000617316.2:c.546C>T

Variant names:

Variant summary

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

The ENST00000617316.2(ORAI1):c.546C>T(p.Ile182Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 1,614,070 control chromosomes in the GnomAD database, including 27,597 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2215 hom., cov: 33)

Exomes 𝑓: 0.18 ( 25382 hom. )

Consequence

ORAI1
ENST00000617316.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4O:1

Conservation

PhyloP100: -0.831

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 12-121641283-C-T is Benign according to our data. Variant chr12-121641283-C-T is described in ClinVar as [Benign]. Clinvar id is 379393.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.831 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ORAI1	NR_186857.1 link	n.764C>T		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	Protein	UniProt
ORAI1	ENST00000617316.2 link	c.546C>T	p.Ile182Ile	synonymous_variant	Exon 3 of 3	1	ENSP00000482568.2	Q96D31-1
ORAI1	ENST00000611718.1 link	n.602C>T		non_coding_transcript_exon_variant	Exon 2 of 2	5
ORAI1	ENST00000646827.1 link	n.744C>T		non_coding_transcript_exon_variant	Exon 2 of 2
ORAI1	ENST00000698901.1 link	n.668C>T		non_coding_transcript_exon_variant	Exon 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.156

AC:

23739

AN:

152110

Hom.:

2209

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0868

Gnomad AMI

AF:

0.259

Gnomad AMR

AF:

0.241

Gnomad ASJ

AF:

0.214

Gnomad EAS

AF:

0.253

Gnomad SAS

AF:

0.327

Gnomad FIN

AF:

0.118

Gnomad MID

AF:

0.234

Gnomad NFE

AF:

0.160

Gnomad OTH

AF:

0.178

GnomAD3 exomes

AF:

0.203

AC:

50725

AN:

249926

Hom.:

5920

AF XY:

0.207

AC XY:

28030

AN XY:

135214

show subpopulations

Gnomad AFR exome

AF:

0.0842

Gnomad AMR exome

AF:

0.300

Gnomad ASJ exome

AF:

0.198

Gnomad EAS exome

AF:

0.258

Gnomad SAS exome

AF:

0.332

Gnomad FIN exome

AF:

0.119

Gnomad NFE exome

AF:

0.163

Gnomad OTH exome

AF:

0.188

GnomAD4 exome

AF:

0.178

AC:

260437

AN:

1461844

Hom.:

25382

Cov.:

AF XY:

0.183

AC XY:

132880

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.0871

Gnomad4 AMR exome

AF:

0.294

Gnomad4 ASJ exome

AF:

0.201

Gnomad4 EAS exome

AF:

0.240

Gnomad4 SAS exome

AF:

0.331

Gnomad4 FIN exome

AF:

0.123

Gnomad4 NFE exome

AF:

0.163

Gnomad4 OTH exome

AF:

0.189

GnomAD4 genome

AF:

0.156

AC:

23783

AN:

152226

Hom.:

2215

Cov.:

AF XY:

0.161

AC XY:

11948

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.0871

Gnomad4 AMR

AF:

0.242

Gnomad4 ASJ

AF:

0.214

Gnomad4 EAS

AF:

0.253

Gnomad4 SAS

AF:

0.326

Gnomad4 FIN

AF:

0.118

Gnomad4 NFE

AF:

0.160

Gnomad4 OTH

AF:

0.181

Alfa

AF:

0.174

Hom.:

3557

Bravo

AF:

0.161

Asia WGS

AF:

0.311

AC:

1081

AN:

3478

EpiCase

AF:

0.177

EpiControl

AF:

0.174

ClinVar

Significance: Benign

Submissions summary: Benign:4Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Oct 20, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 51% of patients studied by a panel of primary immunodeficiencies. Number of patients: 48. Only high quality variants are reported. -

not provided

Benign:1Other:1

GenomeConnect, ClinGen

Significance: not provided

Review Status: no classification provided

Collection Method: phenotyping only

Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

3.4

DANN

Benign

0.79

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