rs917998

Positions:

• chr2-102451696-C-T

Variant summary

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

The NM_001393487.1(IL18RAP):​c.1385-70C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0751 in 1,261,280 control chromosomes in the GnomAD database, including 4,135 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 0.069 (477 hom., cov: 33)
  • Exomes 𝑓: 0.076 (3658 hom.)
• Consequence: IL18RAP NM_001393487.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0770

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 (NFE) allele frequency at 95% confidence interval = 0.0867 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL18RAP	NM_001393487.1	c.1385-70C>T		intron_variant		ENST00000687160.1	NP_001380416.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL18RAP	ENST00000687160.1	c.1385-70C>T		intron_variant			NM_001393487.1	ENSP00000510345	P1
IL18RAP	ENST00000264260.6	c.1385-70C>T		intron_variant		1		ENSP00000264260	P1
IL18RAP	ENST00000409369.1	c.959-70C>T		intron_variant		1		ENSP00000387201

Frequencies

GnomAD3 genomes AF: 0.0694 AC: 10558 AN: 152088 Hom.: 477 Cov.: 33

Gnomad AFR AF: 0.0396

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.0588

Gnomad ASJ AF: 0.0476

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0157

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0886

Gnomad OTH AF: 0.0680

GnomAD4 exome AF: 0.0758 AC: 84107 AN: 1109072 Hom.: 3658 AF XY: 0.0743 AC XY: 41466 AN XY: 558206

Gnomad4 AFR exome AF: 0.0363

Gnomad4 AMR exome AF: 0.0462

Gnomad4 ASJ exome AF: 0.0377

Gnomad4 EAS exome AF: 0.000423

Gnomad4 SAS exome AF: 0.0159

Gnomad4 FIN exome AF: 0.130

Gnomad4 NFE exome AF: 0.0850

Gnomad4 OTH exome AF: 0.0678

GnomAD4 genome AF: 0.0694 AC: 10556 AN: 152208 Hom.: 477 Cov.: 33 AF XY: 0.0702 AC XY: 5228 AN XY: 74424

Gnomad4 AFR AF: 0.0395

Gnomad4 AMR AF: 0.0587

Gnomad4 ASJ AF: 0.0476

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0157

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.0885

Gnomad4 OTH AF: 0.0673

Alfa AF: 0.0784 Hom.: 309

Bravo AF: 0.0618

Asia WGS AF: 0.00895 AC: 32 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	8.0
DANN	Benign	0.53

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: rs917998; hg19: chr2-103068156;