dbSNP rs74808898: ORAI1:n.1577A>G (chr12-121642116-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NR_186857.1(ORAI1):n.1597A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0259 in 198,958 control chromosomes in the GnomAD database, including 212 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.030 ( 179 hom., cov: 32)

Exomes 𝑓: 0.014 ( 33 hom. )

Consequence

ORAI1
NR_186857.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.91

Publications

3 publications found

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 Gene-Disease associations (from GenCC):

tubular aggregate myopathy
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
myopathy, tubular aggregate, 2
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
combined immunodeficiency due to ORAI1 deficiency
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
Stormorken syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ORAI1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NR_186857.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ORAI1	NR_186857.1		n.1597A>G		non_coding_transcript_exon	Exon 2 of 2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ORAI1	ENST00000646827.1		n.1577A>G	non_coding_transcript_exon	Exon 2 of 2
ORAI1	ENST00000698901.2		n.1501A>G	non_coding_transcript_exon	Exon 2 of 2
ORAI1	ENST00000617316.2	TSL:1	c.*473A>G	downstream_gene	N/A	ENSP00000482568.2	Q96D31-1

Frequencies

GnomAD3 genomes

AF:

0.0295

AC:

4496

AN:

152152

Hom.:

178

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0762

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.0123

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.111

Gnomad SAS

AF:

0.0108

Gnomad FIN

AF:

0.00499

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00592

Gnomad OTH

AF:

0.0234

GnomAD4 exome

AF:

0.0139

AC:

649

AN:

46688

Hom.:

Cov.:

AF XY:

0.0125

AC XY:

303

AN XY:

24332

show subpopulations

African (AFR)

AF:

0.0690

AC:

133

AN:

1928

American (AMR)

AF:

0.00588

AC:

AN:

3740

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

964

East Asian (EAS)

AF:

0.0944

AC:

316

AN:

3346

South Asian (SAS)

AF:

0.00443

AC:

AN:

5646

European-Finnish (FIN)

AF:

0.000865

AC:

AN:

1156

Middle Eastern (MID)

AF:

0.00

AC:

AN:

136

European-Non Finnish (NFE)

AF:

0.00462

AC:

127

AN:

27500

Other (OTH)

AF:

0.0110

AC:

AN:

2272

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

123

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0296

AC:

4505

AN:

152270

Hom.:

179

Cov.:

AF XY:

0.0296

AC XY:

2207

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.0762

AC:

3167

AN:

41552

American (AMR)

AF:

0.0122

AC:

187

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00231

AC:

AN:

3470

East Asian (EAS)

AF:

0.112

AC:

578

AN:

5182

South Asian (SAS)

AF:

0.0112

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00499

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00592

AC:

403

AN:

68030

Other (OTH)

AF:

0.0232

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

222

444

665

887

1109

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

192

240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0193

Hom.:

Bravo

AF:

0.0317

Asia WGS

AF:

0.0580

AC:

202

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

5.9

(source)

DANN

Benign

0.70

PhyloP100

1.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over