rs6749014

chr2-102389988-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.950-68C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.474 in 1,507,160 control chromosomes in the GnomAD database, including 178,125 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 (23587 hom., cov: 32)
  • Exomes 𝑓: 0.47 (154538 hom.)
• Consequence: IL18R1 NM_003855.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.961

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=-0.91).
• 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	UniProt
IL18R1	NM_003855.5	c.950-68C>T		intron_variant		ENST00000233957.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL18R1	ENST00000233957.7	c.950-68C>T		intron_variant		5	NM_003855.5	P1
IL18R1	ENST00000409599.5	c.950-68C>T		intron_variant		5		P1
IL18R1	ENST00000410040.5	c.950-68C>T		intron_variant		2
IL18R1	ENST00000677287.1	c.*494-68C>T		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.535 AC: 81224 AN: 151916 Hom.: 23556 Cov.: 32

Gnomad AFR AF: 0.732

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.615

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.543

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.526

GnomAD4 exome AF: 0.467 AC: 632726 AN: 1355126 Hom.: 154538 AF XY: 0.460 AC XY: 310621 AN XY: 674604

Gnomad4 AFR exome AF: 0.747

Gnomad4 AMR exome AF: 0.294

Gnomad4 ASJ exome AF: 0.612

Gnomad4 EAS exome AF: 0.168

Gnomad4 SAS exome AF: 0.260

Gnomad4 FIN exome AF: 0.534

Gnomad4 NFE exome AF: 0.485

Gnomad4 OTH exome AF: 0.479

GnomAD4 genome AF: 0.535 AC: 81308 AN: 152034 Hom.: 23587 Cov.: 32 AF XY: 0.529 AC XY: 39276 AN XY: 74302

Gnomad4 AFR AF: 0.732

Gnomad4 AMR AF: 0.413

Gnomad4 ASJ AF: 0.615

Gnomad4 EAS AF: 0.150

Gnomad4 SAS AF: 0.266

Gnomad4 FIN AF: 0.543

Gnomad4 NFE AF: 0.486

Gnomad4 OTH AF: 0.522

Alfa AF: 0.485 Hom.: 4101

Bravo AF: 0.535

Asia WGS AF: 0.232 AC: 809 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.12
Dann	Benign	0.77

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: rs6749014; hg19: chr2-103006448; COSMIC: COSV52123151;