Variant rs712853 details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000617316.2(ORAI1):c.*119A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 1,321,178 control chromosomes in the GnomAD database, including 51,898 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 10925 hom., cov: 34)

Exomes 𝑓: 0.25 ( 40973 hom. )

Consequence

ORAI1
ENST00000617316.2 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.696

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:

ORAI1 (HGNC:):

ORAI1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 12-121641762-A-G is Benign according to our data. Variant chr12-121641762-A-G is described in ClinVar as [Benign]. Clinvar id is 1263731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.585 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ORAI1	NR_186857.1 linkuse as main transcript	n.1243A>G		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	Protein	UniProt
ORAI1	ENST00000617316.2 linkuse as main transcript	c.*119A>G	3_prime_UTR_variant	3/3	1	ENSP00000482568.2	Q96D31-1
ORAI1	ENST00000646827.1 linkuse as main transcript	n.1223A>G	non_coding_transcript_exon_variant	2/2
ORAI1	ENST00000698901.1 linkuse as main transcript	n.1147A>G	non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes

AF:

0.348

AC:

52311

AN:

150270

Hom.:

10897

Cov.:

show subpopulations

Gnomad AFR

AF:

0.591

Gnomad AMI

AF:

0.154

Gnomad AMR

AF:

0.232

Gnomad ASJ

AF:

0.159

Gnomad EAS

AF:

0.342

Gnomad SAS

AF:

0.198

Gnomad FIN

AF:

0.307

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.257

Gnomad OTH

AF:

0.283

GnomAD4 exome

AF:

0.254

AC:

297738

AN:

1170790

Hom.:

40973

Cov.:

AF XY:

0.251

AC XY:

148418

AN XY:

591646

show subpopulations

Gnomad4 AFR exome

AF:

0.596

Gnomad4 AMR exome

AF:

0.190

Gnomad4 ASJ exome

AF:

0.160

Gnomad4 EAS exome

AF:

0.368

Gnomad4 SAS exome

AF:

0.178

Gnomad4 FIN exome

AF:

0.297

Gnomad4 NFE exome

AF:

0.250

Gnomad4 OTH exome

AF:

0.246

GnomAD4 genome

AF:

0.348

AC:

52387

AN:

150388

Hom.:

10925

Cov.:

AF XY:

0.345

AC XY:

25306

AN XY:

73398

show subpopulations

Gnomad4 AFR

AF:

0.591

Gnomad4 AMR

AF:

0.232

Gnomad4 ASJ

AF:

0.159

Gnomad4 EAS

AF:

0.343

Gnomad4 SAS

AF:

0.199

Gnomad4 FIN

AF:

0.307

Gnomad4 NFE

AF:

0.257

Gnomad4 OTH

AF:

0.281

Alfa

AF:

0.251

Hom.:

4021

Bravo

AF:

0.349

Asia WGS

AF:

0.266

AC:

928

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 07, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

8.2

DANN

Benign

0.69

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