rs11548651

Variant names:

• chr12-121641693-T-A
• rs11548651
• ENST00000617316.2:c.*50T>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.579
• Publications: 5 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000617316.2. 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.1174T>A		non_coding_transcript_exon	Exon 2 of 2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ORAI1	ENST00000617316.2	TSL:1	c.*50T>A		3_prime_UTR	Exon 3 of 3	ENSP00000482568.2	Q96D31-1
	ORAI1	ENST00000646827.1		n.1154T>A		non_coding_transcript_exon	Exon 2 of 2
	ORAI1	ENST00000698901.2		n.1078T>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.0296 AC: 4511 AN: 152198 Hom.: 179 Cov.: 34

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

GnomAD2 exomes AF: 0.0169 AC: 4001 AN: 237222 AF XY: 0.0150

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 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.: 34 AF XY: 0.0120 AC XY: 8642 AN XY: 721294

African (AFR) AF: 0.0805 AC: 2693 AN: 33466

American (AMR) AF: 0.00666 AC: 298 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00214 AC: 56 AN: 26136

East Asian (EAS) AF: 0.149 AC: 5899 AN: 39694

South Asian (SAS) AF: 0.00699 AC: 603 AN: 86232

European-Finnish (FIN) AF: 0.00536 AC: 221 AN: 41196

Middle Eastern (MID) AF: 0.00875 AC: 49 AN: 5600

European-Non Finnish (NFE) AF: 0.00643 AC: 7144 AN: 1111732

Other (OTH) AF: 0.0155 AC: 932 AN: 60300

GnomAD4 genome AF: 0.0297 AC: 4520 AN: 152316 Hom.: 180 Cov.: 34 AF XY: 0.0297 AC XY: 2213 AN XY: 74478

African (AFR) AF: 0.0765 AC: 3180 AN: 41578

American (AMR) AF: 0.0122 AC: 186 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00231 AC: 8 AN: 3470

East Asian (EAS) AF: 0.111 AC: 577 AN: 5176

South Asian (SAS) AF: 0.0120 AC: 58 AN: 4832

European-Finnish (FIN) AF: 0.00489 AC: 52 AN: 10624

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00594 AC: 404 AN: 68016

Other (OTH) AF: 0.0232 AC: 49 AN: 2114

Alfa AF: 0.0141 Hom.: 12

Bravo AF: 0.0318

Asia WGS AF: 0.0590 AC: 204 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.47
DANN	Benign	0.88
PhyloP100		-0.58
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs11548651;

hg19: chr12-122079599;