2-102441432-A-G

Position:

• chr2-102441432-A-G

Variant summary

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

The NM_001393487.1(IL18RAP):​c.796+55A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 1,383,484 control chromosomes in the GnomAD database, including 13,148 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 0.11 (1174 hom., cov: 32)
  • Exomes 𝑓: 0.13 (11974 hom.)
• Consequence: IL18RAP NM_001393487.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.52

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL18RAP	NM_001393487.1	c.796+55A>G		intron_variant		ENST00000687160.1	NP_001380416.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL18RAP	ENST00000687160.1	c.796+55A>G		intron_variant			NM_001393487.1	ENSP00000510345	P1
IL18RAP	ENST00000264260.6	c.796+55A>G		intron_variant		1		ENSP00000264260	P1
IL18RAP	ENST00000409369.1	c.370+55A>G		intron_variant		1		ENSP00000387201

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17507 AN: 152126 Hom.: 1174 Cov.: 32

Gnomad AFR AF: 0.0647

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.0142

Gnomad SAS AF: 0.0656

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.125

GnomAD4 exome AF: 0.133 AC: 163994 AN: 1231240 Hom.: 11974 AF XY: 0.132 AC XY: 81968 AN XY: 623160

Gnomad4 AFR exome AF: 0.0671

Gnomad4 AMR exome AF: 0.0763

Gnomad4 ASJ exome AF: 0.222

Gnomad4 EAS exome AF: 0.00799

Gnomad4 SAS exome AF: 0.0576

Gnomad4 FIN exome AF: 0.170

Gnomad4 NFE exome AF: 0.146

Gnomad4 OTH exome AF: 0.129

GnomAD4 genome AF: 0.115 AC: 17507 AN: 152244 Hom.: 1174 Cov.: 32 AF XY: 0.114 AC XY: 8494 AN XY: 74440

Gnomad4 AFR AF: 0.0647

Gnomad4 AMR AF: 0.102

Gnomad4 ASJ AF: 0.211

Gnomad4 EAS AF: 0.0143

Gnomad4 SAS AF: 0.0657

Gnomad4 FIN AF: 0.174

Gnomad4 NFE AF: 0.145

Gnomad4 OTH AF: 0.122

Alfa AF: 0.139 Hom.: 1471

Bravo AF: 0.107

Asia WGS AF: 0.0380 AC: 134 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.4
DANN	Benign	0.47

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: rs11465702; hg19: chr2-103057892; COSMIC: COSV51824919; COSMIC: COSV51824919;