GeneBe

rs1555322544

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM2PM4BP6_Moderate

The ENST00000617316.2(ORAI1):​c.132_137delACCGCC​(p.Pro45_Pro46del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. P44P) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 31)

Consequence

ORAI1
ENST00000617316.2 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.187
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in ENST00000617316.2.
BP6
Variant 12-121626873-CCCGCCA-C is Benign according to our data. Variant chr12-121626873-CCCGCCA-C is described in ClinVar as [Benign]. Clinvar id is 2577169.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-121626873-CCCGCCA-C is described in Lovd as [Benign].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ORAI1NR_186857.1 linkn.350_355delACCGCC 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.132_137delACCGCC p.Pro45_Pro46del disruptive_inframe_deletion Exon 2 of 3 1 ENSP00000482568.2 Q96D31-1
ORAI1ENST00000611718.1 linkn.64_69delACCGCC non_coding_transcript_exon_variant Exon 1 of 2 5
ORAI1ENST00000646827.1 linkn.330_335delACCGCC non_coding_transcript_exon_variant Exon 1 of 2
ORAI1ENST00000698901.1 linkn.371_376delACCGCC non_coding_transcript_exon_variant Exon 1 of 2

Frequencies

GnomAD3 genomes
Cov.:
31
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
Cov.:
31

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Jul 11, 2023
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

Variant summary: ORAI1 c.138_143delACCGCC (p.Pro48_Pro49del) results in an in-frame deletion that is predicted to remove two amino acids from the encoded protein. The variant allele was found at a frequency of 0.99 in 194348 control chromosomes, suggesting that it is the major allele and therefore benign. To our knowledge, no occurrence of c.138_143delACCGCC in individuals affected with Myopathy, Tubular Aggregate, 2 and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as benign. -

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