rs2293225

Positions:

• chr2-102419429-C-T

Variant summary

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

The ENST00000264260.6(IL18RAP):​c.-337-132C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 152,174 control chromosomes in the GnomAD database, including 2,469 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 0.16 (2467 hom., cov: 32)
  • Exomes 𝑓: 0.16 (2 hom.)
• Consequence: IL18RAP ENST00000264260.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0810

Genes affected

IL18RAP (HGNC:5989): (interleukin 18 receptor accessory protein) The protein encoded by this gene is an accessory subunit of the heterodimeric receptor for interleukin 18 (IL18), a proinflammatory cytokine involved in inducing cell-mediated immunity. This protein enhances the IL18-binding activity of the IL18 receptor and plays a role in signaling by IL18. Mutations in this gene are associated with Crohn's disease and inflammatory bowel disease, and susceptibility to celiac disease and leprosy. Alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known. [provided by RefSeq, Feb 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL18RAP	NM_001393486.1	c.-337-132C>T		intron_variant			NP_001380415.1
IL18RAP	NM_001393488.1	c.-967-132C>T		intron_variant			NP_001380417.1
IL18RAP	NM_001393489.1	c.-438-132C>T		intron_variant			NP_001380418.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL18RAP	ENST00000264260.6	c.-337-132C>T		intron_variant		1		ENSP00000264260	P1
IL18RAP	ENST00000450855.1			upstream_gene_variant		4		ENSP00000389815

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25080 AN: 151932 Hom.: 2466 Cov.: 32

Gnomad AFR AF: 0.0670

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.170

GnomAD4 exome AF: 0.156 AC: 19 AN: 122 Hom.: 2 Cov.: 0 AF XY: 0.153 AC XY: 11 AN XY: 72

Gnomad4 EAS exome AF: 0.161

Gnomad4 NFE exome AF: 0.100

GnomAD4 genome AF: 0.165 AC: 25085 AN: 152052 Hom.: 2467 Cov.: 32 AF XY: 0.166 AC XY: 12301 AN XY: 74310

Gnomad4 AFR AF: 0.0668

Gnomad4 AMR AF: 0.144

Gnomad4 ASJ AF: 0.129

Gnomad4 EAS AF: 0.230

Gnomad4 SAS AF: 0.227

Gnomad4 FIN AF: 0.207

Gnomad4 NFE AF: 0.215

Gnomad4 OTH AF: 0.178

Alfa AF: 0.193 Hom.: 740

Bravo AF: 0.155

Asia WGS AF: 0.245 AC: 853 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.1
DANN	Benign	0.77

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: rs2293225; hg19: chr2-103035889;