rs10206753

Variant names:

• chr2-102351902-T-C
• rs10206753
• NM_016232.5:c.1652T>C

Your query was ambiguous. Multiple possible variants found:

• chr2-102351902-T-C
• chr2-102351902-T-G

Variant summary

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

The NM_016232.5(IL1RL1):​c.1652T>C​(p.Leu551Ser) 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 1,607,608 control chromosomes in the GnomAD database, including 122,423 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 (17659 hom., cov: 31)
  • Exomes 𝑓: 0.37 (104764 hom.)
• Consequence: IL1RL1 NM_016232.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.346
• 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=3.3796666E-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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RL1	NM_016232.5	MANE Select	c.1652T>C	p.Leu551Ser	missense	Exon 11 of 11	NP_057316.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RL1	ENST00000233954.6	TSL:1 MANE Select	c.1652T>C	p.Leu551Ser	missense	Exon 11 of 11	ENSP00000233954.1
	IL1RL1	ENST00000908526.1		c.1652T>C	p.Leu551Ser	missense	Exon 12 of 12	ENSP00000578585.1
	IL1RL1	ENST00000908527.1		c.1652T>C	p.Leu551Ser	missense	Exon 11 of 11	ENSP00000578586.1

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68417 AN: 151758 Hom.: 17630 Cov.: 31

Gnomad AFR AF: 0.701

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.477

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.413

GnomAD2 exomes AF: 0.340 AC: 84245 AN: 247912 AF XY: 0.332

Gnomad AFR exome AF: 0.710

Gnomad AMR exome AF: 0.218

Gnomad ASJ exome AF: 0.461

Gnomad EAS exome AF: 0.115

Gnomad FIN exome AF: 0.416

Gnomad NFE exome AF: 0.379

Gnomad OTH exome AF: 0.370

GnomAD4 exome AF: 0.368 AC: 535882 AN: 1455732 Hom.: 104764 Cov.: 36 AF XY: 0.362 AC XY: 261983 AN XY: 724322

African (AFR) AF: 0.714 AC: 23769 AN: 33284

American (AMR) AF: 0.230 AC: 10239 AN: 44554

Ashkenazi Jewish (ASJ) AF: 0.468 AC: 12095 AN: 25854

East Asian (EAS) AF: 0.150 AC: 5956 AN: 39662

South Asian (SAS) AF: 0.183 AC: 15748 AN: 85928

European-Finnish (FIN) AF: 0.414 AC: 22065 AN: 53274

Middle Eastern (MID) AF: 0.282 AC: 1514 AN: 5360

European-Non Finnish (NFE) AF: 0.381 AC: 422193 AN: 1107676

Other (OTH) AF: 0.371 AC: 22303 AN: 60140

GnomAD4 genome AF: 0.451 AC: 68496 AN: 151876 Hom.: 17659 Cov.: 31 AF XY: 0.444 AC XY: 32944 AN XY: 74224

African (AFR) AF: 0.701 AC: 29021 AN: 41398

American (AMR) AF: 0.318 AC: 4849 AN: 15272

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

East Asian (EAS) AF: 0.128 AC: 664 AN: 5168

South Asian (SAS) AF: 0.200 AC: 964 AN: 4828

European-Finnish (FIN) AF: 0.421 AC: 4425 AN: 10522

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

European-Non Finnish (NFE) AF: 0.377 AC: 25624 AN: 67918

Other (OTH) AF: 0.409 AC: 861 AN: 2104

Alfa AF: 0.393 Hom.: 31802

Bravo AF: 0.458

TwinsUK AF: 0.380 AC: 1409

ALSPAC AF: 0.378 AC: 1458

ESP6500AA AF: 0.698 AC: 3066

ESP6500EA AF: 0.387 AC: 3324

ExAC AF: 0.348 AC: 42244

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	0.068
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	14
DANN	Benign	0.97
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.070	N
LIST_S2	Benign	0.32	T
MetaRNN	Benign	0.0000034	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.0	L
PhyloP100		0.35
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.13
Sift	Benign	0.13	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.35	B
Vest4		0.058
MPC		0.011
ClinPred		0.0079	T
GERP RS		1.1
Varity_R		0.12
gMVP		0.45
Mutation Taster		=95/5	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: rs10206753; hg19: chr2-102968362; COSMIC: COSV52112943; COSMIC: COSV52112943;