dbSNP rs11548651: ORAI1:c.*50T>A (chr12-121641693-T-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000617316.2(ORAI1):c.*50T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.014 in 1,601,390 control chromosomes in the GnomAD database, including 874 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.030 ( 180 hom., cov: 34)

Exomes 𝑓: 0.012 ( 694 hom. )

Consequence

ORAI1
ENST00000617316.2 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.579

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 12-121641693-T-A is Benign according to our data. Variant chr12-121641693-T-A is described in ClinVar as [Benign]. Clinvar id is 1227827.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
ORAI1	NR_186857.1 link	n.1174T>A		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
ORAI1	ENST00000617316.2 link	c.*50T>A	3_prime_UTR_variant	Exon 3 of 3	1	ENSP00000482568.2	Q96D31-1
ORAI1	ENST00000646827.1 link	n.1154T>A	non_coding_transcript_exon_variant	Exon 2 of 2
ORAI1	ENST00000698901.1 link	n.1078T>A	non_coding_transcript_exon_variant	Exon 2 of 2
ORAI1	ENST00000611718.1 link	n.*160T>A	downstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0296

AC:

4511

AN:

152198

Hom.:

179

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0765

Gnomad AMI

AF:

0.00440

Gnomad AMR

AF:

0.0122

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.111

Gnomad SAS

AF:

0.0116

Gnomad FIN

AF:

0.00489

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00594

Gnomad OTH

AF:

0.0234

GnomAD3 exomes

AF:

0.0169

AC:

4001

AN:

237222

Hom.:

151

AF XY:

0.0150

AC XY:

1956

AN XY:

130312

show subpopulations

Gnomad AFR exome

AF:

0.0781

Gnomad AMR exome

AF:

0.00656

Gnomad ASJ exome

AF:

0.00281

Gnomad EAS exome

AF:

0.0916

Gnomad SAS exome

AF:

0.00635

Gnomad FIN exome

AF:

0.00526

Gnomad NFE exome

AF:

0.00568

Gnomad OTH exome

AF:

0.0124

GnomAD4 exome

AF:

0.0123

AC:

17895

AN:

1449074

Hom.:

694

Cov.:

AF XY:

0.0120

AC XY:

8642

AN XY:

721294

show subpopulations

Gnomad4 AFR exome

AF:

0.0805

Gnomad4 AMR exome

AF:

0.00666

Gnomad4 ASJ exome

AF:

0.00214

Gnomad4 EAS exome

AF:

0.149

Gnomad4 SAS exome

AF:

0.00699

Gnomad4 FIN exome

AF:

0.00536

Gnomad4 NFE exome

AF:

0.00643

Gnomad4 OTH exome

AF:

0.0155

GnomAD4 genome

AF:

0.0297

AC:

4520

AN:

152316

Hom.:

180

Cov.:

AF XY:

0.0297

AC XY:

2213

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0765

Gnomad4 AMR

AF:

0.0122

Gnomad4 ASJ

AF:

0.00231

Gnomad4 EAS

AF:

0.111

Gnomad4 SAS

AF:

0.0120

Gnomad4 FIN

AF:

0.00489

Gnomad4 NFE

AF:

0.00594

Gnomad4 OTH

AF:

0.0232

Alfa

AF:

0.0141

Hom.:

Bravo

AF:

0.0318

Asia WGS

AF:

0.0590

AC:

204

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 07, 2018

GeneDx

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

-0.71

CADD

Benign

0.47

DANN

Benign

0.88

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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