chr2-102442777-T-G

Position:

• chr2-102442777-T-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL18RAP	NM_001393487.1	c.797-423T>G		intron_variant		ENST00000687160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL18RAP	ENST00000687160.1	c.797-423T>G		intron_variant			NM_001393487.1	P1
IL18RAP	ENST00000264260.6	c.797-423T>G		intron_variant		1		P1
IL18RAP	ENST00000409369.1	c.371-423T>G		intron_variant		1

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

Gnomad4 AFR AF: 0.225

Gnomad4 AMR AF: 0.195

Gnomad4 ASJ AF: 0.159

Gnomad4 EAS AF: 0.402

Gnomad4 SAS AF: 0.288

Gnomad4 FIN AF: 0.279

Gnomad4 NFE AF: 0.282

Gnomad4 OTH AF: 0.242

Alfa AF: 0.187 Hom.: 543

Bravo AF: 0.250

Asia WGS AF: 0.350 AC: 1218 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.21
DANN	Benign	0.53

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

Publications

LitVar

Other links and lift over

dbSNP: rs10490203; hg19: chr2-103059237;