2-102384942-C-T

Variant names:

• chr2-102384942-C-T
• rs1035130
• NM_003855.5:c.753C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_003855.5(IL18R1):​c.753C>T​(p.Phe251Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 1,600,312 control chromosomes in the GnomAD database, including 62,186 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 0.24 (4770 hom., cov: 32)
  • Exomes 𝑓: 0.28 (57416 hom.)
• Consequence: IL18R1 NM_003855.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.326
• Publications: 50 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP7: Synonymous conserved (PhyloP=0.326 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.392 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.753C>T	p.Phe251Phe	synonymous	Exon 7 of 11	NP_003846.1	Q13478
	IL18R1	NM_001371418.1		c.753C>T	p.Phe251Phe	synonymous	Exon 7 of 11	NP_001358347.1	B7ZKV7
	IL18R1	NM_001371419.1		c.753C>T	p.Phe251Phe	synonymous	Exon 7 of 9	NP_001358348.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL18R1	ENST00000233957.7	TSL:5 MANE Select	c.753C>T	p.Phe251Phe	synonymous	Exon 7 of 11	ENSP00000233957.1	Q13478
	IL18R1	ENST00000409599.5	TSL:5	c.753C>T	p.Phe251Phe	synonymous	Exon 8 of 12	ENSP00000387211.1	Q13478
	IL18R1	ENST00000410040.5	TSL:2	c.753C>T	p.Phe251Phe	synonymous	Exon 7 of 11	ENSP00000386663.1	Q13478

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36149 AN: 151490 Hom.: 4772 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.220

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.231

GnomAD2 exomes AF: 0.258 AC: 64465 AN: 250070 AF XY: 0.263

Gnomad AFR exome AF: 0.152

Gnomad AMR exome AF: 0.170

Gnomad ASJ exome AF: 0.154

Gnomad EAS exome AF: 0.403

Gnomad FIN exome AF: 0.273

Gnomad NFE exome AF: 0.276

Gnomad OTH exome AF: 0.234

GnomAD4 exome AF: 0.277 AC: 401598 AN: 1448702 Hom.: 57416 Cov.: 30 AF XY: 0.278 AC XY: 200496 AN XY: 721252

African (AFR) AF: 0.147 AC: 4889 AN: 33276

American (AMR) AF: 0.172 AC: 7650 AN: 44440

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 4029 AN: 26054

East Asian (EAS) AF: 0.388 AC: 15299 AN: 39400

South Asian (SAS) AF: 0.282 AC: 24167 AN: 85590

European-Finnish (FIN) AF: 0.276 AC: 14742 AN: 53330

Middle Eastern (MID) AF: 0.177 AC: 1018 AN: 5742

European-Non Finnish (NFE) AF: 0.285 AC: 314030 AN: 1100936

Other (OTH) AF: 0.263 AC: 15774 AN: 59934

GnomAD4 genome AF: 0.238 AC: 36158 AN: 151610 Hom.: 4770 Cov.: 32 AF XY: 0.238 AC XY: 17652 AN XY: 74066

African (AFR) AF: 0.158 AC: 6523 AN: 41306

American (AMR) AF: 0.190 AC: 2899 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 530 AN: 3468

East Asian (EAS) AF: 0.406 AC: 2095 AN: 5154

South Asian (SAS) AF: 0.281 AC: 1350 AN: 4806

European-Finnish (FIN) AF: 0.272 AC: 2833 AN: 10422

Middle Eastern (MID) AF: 0.202 AC: 59 AN: 292

European-Non Finnish (NFE) AF: 0.282 AC: 19182 AN: 67904

Other (OTH) AF: 0.238 AC: 499 AN: 2098

Alfa AF: 0.255 Hom.: 9913

Bravo AF: 0.227

Asia WGS AF: 0.349 AC: 1213 AN: 3476

EpiCase AF: 0.269

EpiControl AF: 0.270

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.6
DANN	Benign	0.50
PhyloP100		0.33
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1035130; hg19: chr2-103001402; COSMIC: COSV52122702;