12-121638011-T-C

Position:

• chr12-121638011-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032790.3(ORAI1):​c.307-3030T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 152,200 control chromosomes in the GnomAD database, including 5,698 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.26 (5698 hom., cov: 32)
• Consequence: ORAI1 NM_032790.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ORAI1	NM_032790.3	c.307-3030T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ORAI1	ENST00000617316.2	c.304-3030T>C		intron_variant		1		P1
ORAI1	ENST00000611718.1	n.360-3030T>C		intron_variant, non_coding_transcript_variant		5
ORAI1	ENST00000646827.1	n.502-3030T>C		intron_variant, non_coding_transcript_variant
ORAI1	ENST00000698901.1	n.426-3030T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39600 AN: 152082 Hom.: 5678 Cov.: 32

Gnomad AFR AF: 0.335

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.253

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.261 AC: 39686 AN: 152200 Hom.: 5698 Cov.: 32 AF XY: 0.264 AC XY: 19635 AN XY: 74410

Gnomad4 AFR AF: 0.336

Gnomad4 AMR AF: 0.294

Gnomad4 ASJ AF: 0.253

Gnomad4 EAS AF: 0.399

Gnomad4 SAS AF: 0.379

Gnomad4 FIN AF: 0.152

Gnomad4 NFE AF: 0.206

Gnomad4 OTH AF: 0.256

Alfa AF: 0.237 Hom.: 2342

Bravo AF: 0.272

Asia WGS AF: 0.414 AC: 1437 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.091
DANN	Benign	0.41

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: rs6486795; hg19: chr12-122075917;