rs2272128

Positions:

• chr2-102423469-G-A
• chr2-102423469-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001393487.1(IL18RAP):​c.70+122G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 896,870 control chromosomes in the GnomAD database, including 248,947 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 0.77 (46418 hom., cov: 32)
  • Exomes 𝑓: 0.73 (202529 hom.)
• Consequence: IL18RAP NM_001393487.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL18RAP	NM_001393487.1	c.70+122G>A		intron_variant		ENST00000687160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL18RAP	ENST00000687160.1	c.70+122G>A		intron_variant			NM_001393487.1	P1

Frequencies

GnomAD3 genomes AF: 0.773 AC: 117490 AN: 152044 Hom.: 46371 Cov.: 32

Gnomad AFR AF: 0.889

Gnomad AMI AF: 0.674

Gnomad AMR AF: 0.604

Gnomad ASJ AF: 0.767

Gnomad EAS AF: 0.552

Gnomad SAS AF: 0.551

Gnomad FIN AF: 0.812

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.768

Gnomad OTH AF: 0.756

GnomAD4 exome AF: 0.729 AC: 543144 AN: 744706 Hom.: 202529 AF XY: 0.722 AC XY: 283883 AN XY: 393030

Gnomad4 AFR exome AF: 0.893

Gnomad4 AMR exome AF: 0.463

Gnomad4 ASJ exome AF: 0.768

Gnomad4 EAS exome AF: 0.553

Gnomad4 SAS exome AF: 0.549

Gnomad4 FIN exome AF: 0.812

Gnomad4 NFE exome AF: 0.771

Gnomad4 OTH exome AF: 0.742

GnomAD4 genome AF: 0.773 AC: 117588 AN: 152164 Hom.: 46418 Cov.: 32 AF XY: 0.767 AC XY: 57005 AN XY: 74370

Gnomad4 AFR AF: 0.889

Gnomad4 AMR AF: 0.603

Gnomad4 ASJ AF: 0.767

Gnomad4 EAS AF: 0.553

Gnomad4 SAS AF: 0.551

Gnomad4 FIN AF: 0.812

Gnomad4 NFE AF: 0.768

Gnomad4 OTH AF: 0.759

Alfa AF: 0.744 Hom.: 22408

Bravo AF: 0.762

Asia WGS AF: 0.582 AC: 2024 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.020
DANN	Benign	0.38

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: rs2272128; hg19: chr2-103039929; COSMIC: COSV51824712;