rs74808898

Positions:

• chr12-121642116-A-G

Variant summary

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

The NR_186857.1(ORAI1):​n.1597A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0259 in 198,958 control chromosomes in the GnomAD database, including 212 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 0.030 (179 hom., cov: 32)
  • Exomes 𝑓: 0.014 (33 hom.)
• Consequence: ORAI1 NR_186857.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.91

Genes affected

ORAI1 (HGNC:):

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 = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ORAI1	NR_186857.1	n.1597A>G		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ORAI1	ENST00000646827.1	n.1577A>G		non_coding_transcript_exon_variant	2/2
ORAI1	ENST00000698901.1	n.1501A>G		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes AF: 0.0295 AC: 4496 AN: 152152 Hom.: 178 Cov.: 32

Gnomad AFR AF: 0.0762

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0123

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.0108

Gnomad FIN AF: 0.00499

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00592

Gnomad OTH AF: 0.0234

GnomAD4 exome AF: 0.0139 AC: 649 AN: 46688 Hom.: 33 Cov.: 0 AF XY: 0.0125 AC XY: 303 AN XY: 24332

Gnomad4 AFR exome AF: 0.0690

Gnomad4 AMR exome AF: 0.00588

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0944

Gnomad4 SAS exome AF: 0.00443

Gnomad4 FIN exome AF: 0.000865

Gnomad4 NFE exome AF: 0.00462

Gnomad4 OTH exome AF: 0.0110

GnomAD4 genome AF: 0.0296 AC: 4505 AN: 152270 Hom.: 179 Cov.: 32 AF XY: 0.0296 AC XY: 2207 AN XY: 74442

Gnomad4 AFR AF: 0.0762

Gnomad4 AMR AF: 0.0122

Gnomad4 ASJ AF: 0.00231

Gnomad4 EAS AF: 0.112

Gnomad4 SAS AF: 0.0112

Gnomad4 FIN AF: 0.00499

Gnomad4 NFE AF: 0.00592

Gnomad4 OTH AF: 0.0232

Alfa AF: 0.0172 Hom.: 12

Bravo AF: 0.0317

Asia WGS AF: 0.0580 AC: 202 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	5.9
DANN	Benign	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs74808898; hg19: chr12-122080022;