2-102351896-C-T

Variant names:

• chr2-102351896-C-T
• rs10192157
• NM_016232.5:c.1646C>T

Variant summary

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

The NM_016232.5(IL1RL1):​c.1646C>T​(p.Thr549Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 1,608,344 control chromosomes in the GnomAD database, including 122,500 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.45 (17648 hom., cov: 31)
  • Exomes 𝑓: 0.37 (104852 hom.)
• Consequence: IL1RL1 NM_016232.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72
• Publications: 59 publications found

Genes affected

IL1RL1 (HGNC:5998): (interleukin 1 receptor like 1) The protein encoded by this gene is a member of the interleukin 1 receptor family. Studies of the similar gene in mouse suggested that this receptor can be induced by proinflammatory stimuli, and may be involved in the function of helper T cells. This gene, interleukin 1 receptor, type I (IL1R1), interleukin 1 receptor, type II (IL1R2) and interleukin 1 receptor-like 2 (IL1RL2) form a cytokine receptor gene cluster in a region mapped to chromosome 2q12. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2008]

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 (MetaRNN=2.4943351E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.694 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016232.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RL1	NM_016232.5	MANE Select	c.1646C>T	p.Thr549Ile	missense	Exon 11 of 11	NP_057316.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RL1	ENST00000233954.6	TSL:1 MANE Select	c.1646C>T	p.Thr549Ile	missense	Exon 11 of 11	ENSP00000233954.1
	IL18R1	ENST00000410040.5	TSL:2	c.-28-10737C>T		intron	N/A	ENSP00000386663.1

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68387 AN: 151700 Hom.: 17619 Cov.: 31

Gnomad AFR AF: 0.701

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.477

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.414

GnomAD2 exomes AF: 0.340 AC: 84564 AN: 248718 AF XY: 0.332

Gnomad AFR exome AF: 0.710

Gnomad AMR exome AF: 0.218

Gnomad ASJ exome AF: 0.463

Gnomad EAS exome AF: 0.115

Gnomad FIN exome AF: 0.416

Gnomad NFE exome AF: 0.379

Gnomad OTH exome AF: 0.371

GnomAD4 exome AF: 0.368 AC: 536246 AN: 1456526 Hom.: 104852 Cov.: 36 AF XY: 0.362 AC XY: 262169 AN XY: 724708

African (AFR) AF: 0.714 AC: 23791 AN: 33322

American (AMR) AF: 0.230 AC: 10257 AN: 44598

Ashkenazi Jewish (ASJ) AF: 0.469 AC: 12150 AN: 25932

East Asian (EAS) AF: 0.150 AC: 5956 AN: 39660

South Asian (SAS) AF: 0.183 AC: 15773 AN: 86024

European-Finnish (FIN) AF: 0.414 AC: 22091 AN: 53328

Middle Eastern (MID) AF: 0.284 AC: 1549 AN: 5450

European-Non Finnish (NFE) AF: 0.381 AC: 422370 AN: 1108042

Other (OTH) AF: 0.371 AC: 22309 AN: 60170

GnomAD4 genome AF: 0.451 AC: 68466 AN: 151818 Hom.: 17648 Cov.: 31 AF XY: 0.444 AC XY: 32915 AN XY: 74172

African (AFR) AF: 0.701 AC: 29013 AN: 41396

American (AMR) AF: 0.318 AC: 4851 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.477 AC: 1653 AN: 3468

East Asian (EAS) AF: 0.128 AC: 661 AN: 5162

South Asian (SAS) AF: 0.200 AC: 963 AN: 4826

European-Finnish (FIN) AF: 0.420 AC: 4412 AN: 10508

Middle Eastern (MID) AF: 0.243 AC: 71 AN: 292

European-Non Finnish (NFE) AF: 0.377 AC: 25618 AN: 67896

Other (OTH) AF: 0.410 AC: 859 AN: 2096

Alfa AF: 0.395 Hom.: 43245

Bravo AF: 0.458

TwinsUK AF: 0.380 AC: 1409

ALSPAC AF: 0.379 AC: 1459

ESP6500AA AF: 0.699 AC: 3076

ESP6500EA AF: 0.388 AC: 3333

ExAC AF: 0.348 AC: 42250

Asia WGS AF: 0.180 AC: 626 AN: 3478

EpiCase AF: 0.380

EpiControl AF: 0.383

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	6.2
DANN	Benign	0.97
DEOGEN2	Benign	0.045	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0092	N
LIST_S2	Benign	0.43	T
MetaRNN	Benign	0.0000025	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.14	N
PhyloP100		-1.7
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.25	N
REVEL	Benign	0.012
Sift	Benign	0.13	T
Sift4G	Benign	0.12	T
Polyphen		0.063	B
Vest4		0.034
MPC		0.011
ClinPred		0.0030	T
GERP RS		-0.89
Varity_R		0.049
gMVP		0.32
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: rs10192157; hg19: chr2-102968356; COSMIC: COSV52112934; COSMIC: COSV52112934;