2-102443564-T-A

Variant summary

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

The NM_001393487.1(IL18RAP):c.920+241T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.776 in 152,108 control chromosomes in the GnomAD database, including 46,872 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency: Genomes: 𝑓 0.78 (46872 hom., cov: 31)
• Consequence: IL18RAP NM_001393487.1 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: 0.189

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.894 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL18RAP	NM_001393487.1	c.920+241T>A		intron_variant		ENST00000687160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL18RAP	ENST00000687160.1	c.920+241T>A		intron_variant			NM_001393487.1	P1
IL18RAP	ENST00000264260.6	c.920+241T>A		intron_variant		1		P1
IL18RAP	ENST00000409369.1	c.494+241T>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.776 AC: 117997 AN: 151988 Hom.: 46829 Cov.: 31

Gnomad AFR AF: 0.902

Gnomad AMI AF: 0.741

Gnomad AMR AF: 0.605

Gnomad ASJ AF: 0.768

Gnomad EAS AF: 0.551

Gnomad SAS AF: 0.558

Gnomad FIN AF: 0.812

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.767

Gnomad OTH AF: 0.754

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.776 AC: 118089 AN: 152108 Hom.: 46872 Cov.: 31 AF XY: 0.770 AC XY: 57267 AN XY: 74326

Gnomad4 AFR AF: 0.902

Gnomad4 AMR AF: 0.604

Gnomad4 ASJ AF: 0.768

Gnomad4 EAS AF: 0.551

Gnomad4 SAS AF: 0.559

Gnomad4 FIN AF: 0.812

Gnomad4 NFE AF: 0.767

Gnomad4 OTH AF: 0.757

Alfa AF: 0.773 Hom.: 5714

Bravo AF: 0.766

Asia WGS AF: 0.580 AC: 2019 AN: 3478

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Ascending aortic dissection Other:1

association, no assertion criteria provided

case-control

Beijing Anzhen Hospital, Capital Medical University

Feb 01, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	1.5
Dann	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs1558650; hg19: chr2-103060024; COSMIC: COSV51824947; COSMIC: COSV51824947;