2-102418915-T-C

Position:

• chr2-102418915-T-C

Variant summary

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

The ENST00000264260.6(IL18RAP):​c.-363T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0784 in 152,378 control chromosomes in the GnomAD database, including 563 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 0.078 (563 hom., cov: 33)
  • Exomes 𝑓: 0.11 (0 hom.)
• Consequence: IL18RAP ENST00000264260.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0440

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=-0.68).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0847 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL18RAP	NM_001393486.1	c.-363T>C		5_prime_UTR_variant	2/13
IL18RAP	NM_001393488.1	c.-993T>C		5_prime_UTR_variant	1/12
IL18RAP	NM_001393489.1	c.-464T>C		5_prime_UTR_variant	2/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL18RAP	ENST00000264260.6	c.-363T>C		5_prime_UTR_variant	1/12	1		P1

Frequencies

GnomAD3 genomes AF: 0.0784 AC: 11925 AN: 152122 Hom.: 562 Cov.: 33

Gnomad AFR AF: 0.0534

Gnomad AMI AF: 0.0440

Gnomad AMR AF: 0.0725

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.0404

Gnomad SAS AF: 0.0844

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.0866

Gnomad OTH AF: 0.102

GnomAD4 exome AF: 0.109 AC: 15 AN: 138 Hom.: 0 Cov.: 0 AF XY: 0.132 AC XY: 10 AN XY: 76

Gnomad4 EAS exome AF: 0.109

GnomAD4 genome AF: 0.0784 AC: 11929 AN: 152240 Hom.: 563 Cov.: 33 AF XY: 0.0787 AC XY: 5860 AN XY: 74440

Gnomad4 AFR AF: 0.0534

Gnomad4 AMR AF: 0.0723

Gnomad4 ASJ AF: 0.187

Gnomad4 EAS AF: 0.0403

Gnomad4 SAS AF: 0.0853

Gnomad4 FIN AF: 0.106

Gnomad4 NFE AF: 0.0866

Gnomad4 OTH AF: 0.102

Alfa AF: 0.0801 Hom.: 180

Bravo AF: 0.0745

Asia WGS AF: 0.0740 AC: 254 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	15
DANN	Benign	0.82

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: rs11465673; hg19: chr2-103035375;