GeneBe

12-121626873-CCCGCCA-CCCGCCACCGCCACCGCCGCCA

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4

The ENST00000617316.2(ORAI1):​c.137_138insACCGCCGCCACCGCC​(p.Pro46_Pro47insProProProProPro) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P46P) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 31)

Consequence

ORAI1
ENST00000617316.2 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.158
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in ENST00000617316.2.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ORAI1NR_186857.1 linkn.355_356insACCGCCGCCACCGCC non_coding_transcript_exon_variant Exon 1 of 2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ORAI1ENST00000617316.2 linkc.137_138insACCGCCGCCACCGCC p.Pro46_Pro47insProProProProPro disruptive_inframe_insertion Exon 2 of 3 1 ENSP00000482568.2 Q96D31-1
ORAI1ENST00000611718.1 linkn.69_70insACCGCCGCCACCGCC non_coding_transcript_exon_variant Exon 1 of 2 5
ORAI1ENST00000646827.1 linkn.335_336insACCGCCGCCACCGCC non_coding_transcript_exon_variant Exon 1 of 2
ORAI1ENST00000698901.1 linkn.376_377insACCGCCGCCACCGCC non_coding_transcript_exon_variant Exon 1 of 2

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
34
GnomAD4 genome
Cov.:
31
Alfa
AF:
1.00
Hom.:
2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-122064778; API