rs6708413

Variant names:

• chr2-102446909-G-A
• rs6708413
• NM_001393487.1:c.1073-161G>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.1073-161G>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 152,150 control chromosomes in the GnomAD database, including 46,907 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 (46907 hom., cov: 32)
• Consequence: IL18RAP NM_001393487.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.587
• Publications: 38 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.895 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL18RAP	NM_001393487.1	c.1073-161G>A		intron_variant	Intron 7 of 9	ENST00000687160.1	NP_001380416.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL18RAP	ENST00000687160.1	c.1073-161G>A		intron_variant	Intron 7 of 9		NM_001393487.1	ENSP00000510345.1
IL18RAP	ENST00000264260.6	c.1073-161G>A		intron_variant	Intron 9 of 11	1		ENSP00000264260.2
IL18RAP	ENST00000409369.1	c.647-161G>A		intron_variant	Intron 7 of 9	1		ENSP00000387201.1

Frequencies

GnomAD3 genomes AF: 0.776 AC: 118052 AN: 152032 Hom.: 46864 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: 0.811

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: 118144 AN: 152150 Hom.: 46907 Cov.: 32 AF XY: 0.771 AC XY: 57317 AN XY: 74364

African (AFR) AF: 0.902 AC: 37471 AN: 41534

American (AMR) AF: 0.604 AC: 9222 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.768 AC: 2665 AN: 3470

East Asian (EAS) AF: 0.552 AC: 2853 AN: 5164

South Asian (SAS) AF: 0.559 AC: 2699 AN: 4826

European-Finnish (FIN) AF: 0.811 AC: 8588 AN: 10588

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

European-Non Finnish (NFE) AF: 0.767 AC: 52154 AN: 67976

Other (OTH) AF: 0.757 AC: 1597 AN: 2110

Alfa AF: 0.740 Hom.: 18391

Bravo AF: 0.766

Asia WGS AF: 0.580 AC: 2018 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.057
DANN	Benign	0.19
PhyloP100		-0.59
Mutation Taster		=17/83	disease causing

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: rs6708413; hg19: chr2-103063369; COSMIC: COSV51824496;