rs6706002

Positions:

• chr2-102389644-A-G

Variant summary

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

The NM_003855.5(IL18R1):​c.950-412A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.534 in 151,998 control chromosomes in the GnomAD database, including 23,562 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 (23562 hom., cov: 32)
• Consequence: IL18R1 NM_003855.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.273

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=-0.96).
• 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.950-412A>G		intron_variant		ENST00000233957.7	NP_003846.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL18R1	ENST00000233957.7	c.950-412A>G		intron_variant		5	NM_003855.5	ENSP00000233957	P1
IL18R1	ENST00000409599.5	c.950-412A>G		intron_variant		5		ENSP00000387211	P1
IL18R1	ENST00000410040.5	c.950-412A>G		intron_variant		2		ENSP00000386663
IL18R1	ENST00000677287.1	c.*494-412A>G		intron_variant, NMD_transcript_variant				ENSP00000503023

Frequencies

GnomAD3 genomes AF: 0.534 AC: 81147 AN: 151880 Hom.: 23531 Cov.: 32

Gnomad AFR AF: 0.731

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.613

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.541

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.526

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.534 AC: 81231 AN: 151998 Hom.: 23562 Cov.: 32 AF XY: 0.528 AC XY: 39217 AN XY: 74264

Gnomad4 AFR AF: 0.732

Gnomad4 AMR AF: 0.413

Gnomad4 ASJ AF: 0.613

Gnomad4 EAS AF: 0.150

Gnomad4 SAS AF: 0.265

Gnomad4 FIN AF: 0.541

Gnomad4 NFE AF: 0.486

Gnomad4 OTH AF: 0.521

Alfa AF: 0.473 Hom.: 3262

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	-0.96
CADD	Benign	5.0
DANN	Benign	0.58

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: rs6706002; hg19: chr2-103006104; COSMIC: COSV52123528;