2-102367819-T-C

Variant names:

• chr2-102367819-T-C
• rs1420098
• NM_003855.5:c.59-6T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003855.5(IL18R1):​c.59-6T>C variant causes a splice region, 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, intron
• Scores: Splicing: ADA: 0.0001448
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.558
• Publications: 28 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003855.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL18R1	NM_003855.5	MANE Select	c.59-6T>C		splice_region intron	N/A	NP_003846.1	Q13478
	IL18R1	NM_001371418.1		c.59-6T>C		splice_region intron	N/A	NP_001358347.1	B7ZKV7
	IL18R1	NM_001371419.1		c.59-6T>C		splice_region intron	N/A	NP_001358348.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL18R1	ENST00000233957.7	TSL:5 MANE Select	c.59-6T>C		splice_region intron	N/A	ENSP00000233957.1	Q13478
	IL18R1	ENST00000409599.5	TSL:5	c.59-6T>C		splice_region intron	N/A	ENSP00000387211.1	Q13478
	IL18R1	ENST00000410040.5	TSL:2	c.59-6T>C		splice_region intron	N/A	ENSP00000386663.1	Q13478

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

GnomAD2 exomes AF: 0.355 AC: 86656 AN: 244440 AF XY: 0.363

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 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

African (AFR) AF: 0.230 AC: 7618 AN: 33184

American (AMR) AF: 0.241 AC: 10544 AN: 43840

Ashkenazi Jewish (ASJ) AF: 0.312 AC: 8089 AN: 25956

East Asian (EAS) AF: 0.408 AC: 16149 AN: 39538

South Asian (SAS) AF: 0.373 AC: 31895 AN: 85610

European-Finnish (FIN) AF: 0.397 AC: 21131 AN: 53184

Middle Eastern (MID) AF: 0.486 AC: 2791 AN: 5744

European-Non Finnish (NFE) AF: 0.391 AC: 432503 AN: 1105504

Other (OTH) AF: 0.380 AC: 22803 AN: 60032

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

African (AFR) AF: 0.234 AC: 9699 AN: 41504

American (AMR) AF: 0.290 AC: 4427 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.307 AC: 1065 AN: 3472

East Asian (EAS) AF: 0.429 AC: 2218 AN: 5176

South Asian (SAS) AF: 0.357 AC: 1724 AN: 4826

European-Finnish (FIN) AF: 0.388 AC: 4104 AN: 10570

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.391 AC: 26570 AN: 67970

Other (OTH) AF: 0.365 AC: 772 AN: 2114

Alfa AF: 0.339 Hom.: 8653

Bravo AF: 0.321

Asia WGS AF: 0.411 AC: 1429 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.1
DANN	Benign	0.63
PhyloP100		0.56
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1420098; hg19: chr2-102984279; COSMIC: COSV52126801; COSMIC: COSV52126801;