rs3771150

Variant names:

• chr2-102444391-G-A
• rs3771150
• NM_001393487.1:c.921-798G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001393487.1(IL18RAP):​c.921-798G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 152,020 control chromosomes in the GnomAD database, including 4,417 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 (4417 hom., cov: 32)
• Consequence: IL18RAP NM_001393487.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.124
• Publications: 26 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL18RAP	NM_001393487.1	c.921-798G>A		intron_variant	Intron 6 of 9	ENST00000687160.1	NP_001380416.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL18RAP	ENST00000687160.1	c.921-798G>A		intron_variant	Intron 6 of 9		NM_001393487.1	ENSP00000510345.1
IL18RAP	ENST00000264260.6	c.921-798G>A		intron_variant	Intron 8 of 11	1		ENSP00000264260.2
IL18RAP	ENST00000409369.1	c.495-798G>A		intron_variant	Intron 6 of 9	1		ENSP00000387201.1

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33600 AN: 151900 Hom.: 4417 Cov.: 32

Gnomad AFR AF: 0.0966

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.223

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.214

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

GnomAD4 genome AF: 0.221 AC: 33603 AN: 152020 Hom.: 4417 Cov.: 32 AF XY: 0.222 AC XY: 16467 AN XY: 74296

African (AFR) AF: 0.0963 AC: 3997 AN: 41498

American (AMR) AF: 0.182 AC: 2781 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 541 AN: 3470

East Asian (EAS) AF: 0.401 AC: 2061 AN: 5144

South Asian (SAS) AF: 0.287 AC: 1382 AN: 4814

European-Finnish (FIN) AF: 0.279 AC: 2941 AN: 10544

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.281 AC: 19125 AN: 67960

Other (OTH) AF: 0.221 AC: 467 AN: 2110

Alfa AF: 0.259 Hom.: 9013

Bravo AF: 0.207

Asia WGS AF: 0.340 AC: 1183 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	1.4
DANN	Benign	0.68
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3771150; hg19: chr2-103060851;