chr12-121641776-A-AT

Position:

• chr12-121641776-A-AT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The ENST00000617316.2(ORAI1):​c.*138dup variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 1,123,738 control chromosomes in the GnomAD database, including 19,793 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.16 (2320 hom., cov: 29)
  • Exomes 𝑓: 0.17 (17473 hom.)
• Consequence: ORAI1 ENST00000617316.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ORAI1	NM_032790.3	c.*138dup		3_prime_UTR_variant	3/3		NP_116179.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ORAI1	ENST00000617316.2	c.*138dup		3_prime_UTR_variant	3/3	1		ENSP00000482568	P1
ORAI1	ENST00000646827.1	n.1242dup		non_coding_transcript_exon_variant	2/2
ORAI1	ENST00000698901.1	n.1166dup		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24282 AN: 152106 Hom.: 2314 Cov.: 29

Gnomad AFR AF: 0.0878

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.183

GnomAD4 exome AF: 0.173 AC: 168415 AN: 971514 Hom.: 17473 Cov.: 13 AF XY: 0.180 AC XY: 89211 AN XY: 496116

Gnomad4 AFR exome AF: 0.0814

Gnomad4 AMR exome AF: 0.275

Gnomad4 ASJ exome AF: 0.198

Gnomad4 EAS exome AF: 0.234

Gnomad4 SAS exome AF: 0.323

Gnomad4 FIN exome AF: 0.124

Gnomad4 NFE exome AF: 0.154

Gnomad4 OTH exome AF: 0.182

GnomAD4 genome AF: 0.160 AC: 24327 AN: 152224 Hom.: 2320 Cov.: 29 AF XY: 0.164 AC XY: 12191 AN XY: 74412

Gnomad4 AFR AF: 0.0882

Gnomad4 AMR AF: 0.245

Gnomad4 ASJ AF: 0.220

Gnomad4 EAS AF: 0.253

Gnomad4 SAS AF: 0.328

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.166

Gnomad4 OTH AF: 0.185

Alfa AF: 0.155 Hom.: 213

Bravo AF: 0.164

Asia WGS AF: 0.312 AC: 1085 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs35558190; hg19: chr12-122079682;