rs2272127

chr2-102423413-C-G

Variant summary

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

The NM_001393487.1(IL18RAP):c.70+66C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 1,259,924 control chromosomes in the GnomAD database, including 22,366 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 0.22 (4086 hom., cov: 33)
  • Exomes 𝑓: 0.17 (18280 hom.)
• Consequence: IL18RAP NM_001393487.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.482

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL18RAP	NM_001393487.1	c.70+66C>G		intron_variant		ENST00000687160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL18RAP	ENST00000687160.1	c.70+66C>G		intron_variant			NM_001393487.1	P1

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33058 AN: 151982 Hom.: 4084 Cov.: 33

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.0952

Gnomad SAS AF: 0.0770

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.213

GnomAD4 exome AF: 0.174 AC: 192674 AN: 1107824 Hom.: 18280 AF XY: 0.171 AC XY: 96924 AN XY: 567846

Gnomad4 AFR exome AF: 0.343

Gnomad4 AMR exome AF: 0.115

Gnomad4 ASJ exome AF: 0.260

Gnomad4 EAS exome AF: 0.124

Gnomad4 SAS exome AF: 0.0676

Gnomad4 FIN exome AF: 0.186

Gnomad4 NFE exome AF: 0.180

Gnomad4 OTH exome AF: 0.183

GnomAD4 genome AF: 0.218 AC: 33088 AN: 152100 Hom.: 4086 Cov.: 33 AF XY: 0.214 AC XY: 15913 AN XY: 74358

Gnomad4 AFR AF: 0.328

Gnomad4 AMR AF: 0.171

Gnomad4 ASJ AF: 0.252

Gnomad4 EAS AF: 0.0954

Gnomad4 SAS AF: 0.0764

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.183

Gnomad4 OTH AF: 0.213

Alfa AF: 0.202 Hom.: 428

Bravo AF: 0.219

Asia WGS AF: 0.0940 AC: 327 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	2.0
Dann	Benign	0.39

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: rs2272127; hg19: chr2-103039873; COSMIC: COSV51824506;