rs1555322544

Positions:

• chr12-121626873-C-CCCGCCA

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4

The NM_032790.3(ORAI1):​c.135_140dup​(p.Pro47_Pro48dup) variant causes a inframe insertion, splice region 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.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ORAI1 NM_032790.3 inframe_insertion, splice_region
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.158

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 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 NM_032790.3.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ORAI1	NM_032790.3	c.135_140dup	p.Pro47_Pro48dup	inframe_insertion, splice_region_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ORAI1	ENST00000617316.2	c.132_137dup	p.Pro46_Pro47dup	inframe_insertion	2/3	1		P1
ORAI1	ENST00000611718.1	n.64_69dup		non_coding_transcript_exon_variant	1/2	5
ORAI1	ENST00000646827.1	n.330_335dup		non_coding_transcript_exon_variant	1/2
ORAI1	ENST00000698901.1	n.371_376dup		non_coding_transcript_exon_variant	1/2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Combined immunodeficiency due to ORAI1 deficiency;C4014557:Myopathy, tubular aggregate, 2 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jul 13, 2017

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1555322544; hg19: chr12-122064778;