NM_001393487.1:c.797-423T>G

Variant names:

• chr2-102442777-T-G
• rs10490203
• NM_001393487.1:c.797-423T>G

Variant summary

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

The NM_001393487.1(IL18RAP):​c.797-423T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 152,124 control chromosomes in the GnomAD database, including 5,364 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 0.26 (5364 hom., cov: 32)
• Consequence: IL18RAP NM_001393487.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.70
• Publications: 13 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.387 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.797-423T>G		intron	N/A	NP_001380416.1	O95256-1
	IL18RAP	NM_001393486.1		c.797-423T>G		intron	N/A	NP_001380415.1	O95256-1
	IL18RAP	NM_003853.4		c.797-423T>G		intron	N/A	NP_003844.1	O95256-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL18RAP	ENST00000687160.1	MANE Select	c.797-423T>G		intron	N/A	ENSP00000510345.1	O95256-1
	IL18RAP	ENST00000264260.6	TSL:1	c.797-423T>G		intron	N/A	ENSP00000264260.2	O95256-1
	IL18RAP	ENST00000409369.1	TSL:1	c.371-423T>G		intron	N/A	ENSP00000387201.1	O95256-2

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39261 AN: 152006 Hom.: 5367 Cov.: 32

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.272

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.235

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

GnomAD4 genome AF: 0.258 AC: 39270 AN: 152124 Hom.: 5364 Cov.: 32 AF XY: 0.258 AC XY: 19197 AN XY: 74346

African (AFR) AF: 0.225 AC: 9336 AN: 41490

American (AMR) AF: 0.195 AC: 2985 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 550 AN: 3468

East Asian (EAS) AF: 0.402 AC: 2075 AN: 5168

South Asian (SAS) AF: 0.288 AC: 1391 AN: 4826

European-Finnish (FIN) AF: 0.279 AC: 2954 AN: 10580

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.282 AC: 19159 AN: 67990

Other (OTH) AF: 0.242 AC: 512 AN: 2114

Alfa AF: 0.191 Hom.: 676

Bravo AF: 0.250

Asia WGS AF: 0.350 AC: 1218 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.21
DANN	Benign	0.53
PhyloP100		-1.7
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: rs10490203; hg19: chr2-103059237;