chr2-102452327-G-A

Variant names:

• chr2-102452327-G-A
• rs7559479
• NM_001393487.1:c.*146G>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.*146G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.745 in 735,698 control chromosomes in the GnomAD database, including 208,018 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 0.78 (46910 hom., cov: 32)
  • Exomes 𝑓: 0.74 (161108 hom.)
• Consequence: IL18RAP NM_001393487.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0960
• Publications: 42 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.895 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393487.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL18RAP	NM_001393487.1	MANE Select	c.*146G>A		3_prime_UTR	Exon 10 of 10	NP_001380416.1	O95256-1
	IL18RAP	NM_001393486.1		c.*146G>A		3_prime_UTR	Exon 13 of 13	NP_001380415.1	O95256-1
	IL18RAP	NM_003853.4		c.*146G>A		3_prime_UTR	Exon 12 of 12	NP_003844.1	O95256-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL18RAP	ENST00000687160.1	MANE Select	c.*146G>A		3_prime_UTR	Exon 10 of 10	ENSP00000510345.1	O95256-1
	IL18RAP	ENST00000264260.6	TSL:1	c.*146G>A		3_prime_UTR	Exon 12 of 12	ENSP00000264260.2	O95256-1
	IL18RAP	ENST00000409369.1	TSL:1	c.*146G>A		3_prime_UTR	Exon 10 of 10	ENSP00000387201.1	O95256-2

Frequencies

GnomAD3 genomes AF: 0.776 AC: 118061 AN: 152056 Hom.: 46867 Cov.: 32

Gnomad AFR AF: 0.902

Gnomad AMI AF: 0.741

Gnomad AMR AF: 0.605

Gnomad ASJ AF: 0.768

Gnomad EAS AF: 0.552

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.810

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.767

Gnomad OTH AF: 0.754

GnomAD4 exome AF: 0.737 AC: 430165 AN: 583522 Hom.: 161108 Cov.: 8 AF XY: 0.728 AC XY: 218954 AN XY: 300646

African (AFR) AF: 0.904 AC: 13482 AN: 14906

American (AMR) AF: 0.525 AC: 9196 AN: 17514

Ashkenazi Jewish (ASJ) AF: 0.769 AC: 11202 AN: 14566

East Asian (EAS) AF: 0.556 AC: 17728 AN: 31882

South Asian (SAS) AF: 0.558 AC: 24925 AN: 44664

European-Finnish (FIN) AF: 0.813 AC: 28310 AN: 34802

Middle Eastern (MID) AF: 0.758 AC: 1711 AN: 2258

European-Non Finnish (NFE) AF: 0.767 AC: 300979 AN: 392492

Other (OTH) AF: 0.744 AC: 22632 AN: 30438

GnomAD4 genome AF: 0.776 AC: 118153 AN: 152176 Hom.: 46910 Cov.: 32 AF XY: 0.771 AC XY: 57323 AN XY: 74392

African (AFR) AF: 0.902 AC: 37478 AN: 41540

American (AMR) AF: 0.604 AC: 9228 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.768 AC: 2665 AN: 3472

East Asian (EAS) AF: 0.552 AC: 2841 AN: 5146

South Asian (SAS) AF: 0.559 AC: 2696 AN: 4822

European-Finnish (FIN) AF: 0.810 AC: 8582 AN: 10590

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.767 AC: 52171 AN: 68004

Other (OTH) AF: 0.757 AC: 1595 AN: 2108

Alfa AF: 0.759 Hom.: 58957

Bravo AF: 0.766

Asia WGS AF: 0.579 AC: 2015 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.4
DANN	Benign	0.39
PhyloP100		0.096
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: rs7559479; hg19: chr2-103068787; COSMIC: COSV51830088;