rs1420096

Positions:

• chr2-102394452-C-T

Variant summary

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

The NM_003855.5(IL18R1):​c.1112-17C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 1,570,424 control chromosomes in the GnomAD database, including 185,344 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 0.53 (23574 hom., cov: 31)
  • Exomes 𝑓: 0.47 (161770 hom.)
• Consequence: IL18R1 NM_003855.5 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL18R1	NM_003855.5	c.1112-17C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000233957.7	NP_003846.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL18R1	ENST00000233957.7	c.1112-17C>T		splice_polypyrimidine_tract_variant, intron_variant		5	NM_003855.5	ENSP00000233957	P1
IL18R1	ENST00000409599.5	c.1112-17C>T		splice_polypyrimidine_tract_variant, intron_variant		5		ENSP00000387211	P1
IL18R1	ENST00000410040.5	c.1112-17C>T		splice_polypyrimidine_tract_variant, intron_variant		2		ENSP00000386663
IL18R1	ENST00000677287.1	c.*656-17C>T		splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant				ENSP00000503023

Frequencies

GnomAD3 genomes AF: 0.535 AC: 81178 AN: 151832 Hom.: 23543 Cov.: 31

Gnomad AFR AF: 0.732

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.614

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.542

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.526

GnomAD3 exomes AF: 0.434 AC: 102512 AN: 236108 Hom.: 25395 AF XY: 0.428 AC XY: 54775 AN XY: 127916

Gnomad AFR exome AF: 0.736

Gnomad AMR exome AF: 0.280

Gnomad ASJ exome AF: 0.610

Gnomad EAS exome AF: 0.138

Gnomad SAS exome AF: 0.258

Gnomad FIN exome AF: 0.536

Gnomad NFE exome AF: 0.489

Gnomad OTH exome AF: 0.481

GnomAD4 exome AF: 0.466 AC: 661291 AN: 1418474 Hom.: 161770 Cov.: 25 AF XY: 0.460 AC XY: 324579 AN XY: 705122

Gnomad4 AFR exome AF: 0.746

Gnomad4 AMR exome AF: 0.292

Gnomad4 ASJ exome AF: 0.611

Gnomad4 EAS exome AF: 0.166

Gnomad4 SAS exome AF: 0.260

Gnomad4 FIN exome AF: 0.535

Gnomad4 NFE exome AF: 0.483

Gnomad4 OTH exome AF: 0.478

GnomAD4 genome AF: 0.535 AC: 81262 AN: 151950 Hom.: 23574 Cov.: 31 AF XY: 0.529 AC XY: 39240 AN XY: 74232

Gnomad4 AFR AF: 0.732

Gnomad4 AMR AF: 0.413

Gnomad4 ASJ AF: 0.614

Gnomad4 EAS AF: 0.151

Gnomad4 SAS AF: 0.266

Gnomad4 FIN AF: 0.542

Gnomad4 NFE AF: 0.486

Gnomad4 OTH AF: 0.522

Alfa AF: 0.519 Hom.: 3968

Bravo AF: 0.535

Asia WGS AF: 0.232 AC: 808 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.35
DANN	Benign	0.60

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: rs1420096; hg19: chr2-103010912; COSMIC: COSV52123223;