rs1420098

chr2-102367819-T-Cchr2-102367819-T-G

Variant summary

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

The NM_003855.5(IL18R1):c.59-6T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 1,604,718 control chromosomes in the GnomAD database, including 115,560 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.34 (9022 hom., cov: 32)
  • Exomes 𝑓: 0.38 (106538 hom.)
• Consequence: IL18R1 NM_003855.5 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0001448
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.558

Genes affected

IL18R1 (HGNC:5988): (interleukin 18 receptor 1) The protein encoded by this gene is a cytokine receptor that belongs to the interleukin 1 receptor family. This receptor specifically binds interleukin 18 (IL18), and is essential for IL18 mediated signal transduction. IFN-alpha and IL12 are reported to induce the expression of this receptor in NK and T cells. This gene along with four other members of the interleukin 1 receptor family, including IL1R2, IL1R1, ILRL2 (IL-1Rrp2), and IL1RL1 (T1/ST2), form a gene cluster on chromosome 2q. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL18R1	NM_003855.5	c.59-6T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000233957.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL18R1	ENST00000233957.7	c.59-6T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5	NM_003855.5	P1
IL18R1	ENST00000409599.5	c.59-6T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5		P1
IL18R1	ENST00000410040.5	c.59-6T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		2
IL18R1	ENST00000677287.1	c.59-6T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50953 AN: 152004 Hom.: 9021 Cov.: 32

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.428

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.359

GnomAD3 exomes AF: 0.355 AC: 86656 AN: 244440 Hom.: 15702 AF XY: 0.363 AC XY: 47887 AN XY: 132050

Gnomad AFR exome AF: 0.230

Gnomad AMR exome AF: 0.233

Gnomad ASJ exome AF: 0.316

Gnomad EAS exome AF: 0.429

Gnomad SAS exome AF: 0.376

Gnomad FIN exome AF: 0.394

Gnomad NFE exome AF: 0.387

Gnomad OTH exome AF: 0.358

GnomAD4 exome AF: 0.381 AC: 553523 AN: 1452592 Hom.: 106538 Cov.: 33 AF XY: 0.382 AC XY: 275652 AN XY: 721676

Gnomad4 AFR exome AF: 0.230

Gnomad4 AMR exome AF: 0.241

Gnomad4 ASJ exome AF: 0.312

Gnomad4 EAS exome AF: 0.408

Gnomad4 SAS exome AF: 0.373

Gnomad4 FIN exome AF: 0.397

Gnomad4 NFE exome AF: 0.391

Gnomad4 OTH exome AF: 0.380

GnomAD4 genome AF: 0.335 AC: 50981 AN: 152126 Hom.: 9022 Cov.: 32 AF XY: 0.336 AC XY: 24960 AN XY: 74360

Gnomad4 AFR AF: 0.234

Gnomad4 AMR AF: 0.290

Gnomad4 ASJ AF: 0.307

Gnomad4 EAS AF: 0.429

Gnomad4 SAS AF: 0.357

Gnomad4 FIN AF: 0.388

Gnomad4 NFE AF: 0.391

Gnomad4 OTH AF: 0.365

Alfa AF: 0.358 Hom.: 6242

Bravo AF: 0.321

Asia WGS AF: 0.411 AC: 1429 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	8.1
Dann	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00014
dbscSNV1_RF	Benign	0.016
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: rs1420098; hg19: chr2-102984279; COSMIC: COSV52126801; COSMIC: COSV52126801;