2-102351896-C-T

Position:

• chr2-102351896-C-T

Variant summary

Our verdict is Benign. Variant got -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. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL1RL1	NM_016232.5	c.1646C>T	p.Thr549Ile	missense_variant	11/11	ENST00000233954.6	NP_057316.3
IL1RL1	XM_006712839.4	c.1646C>T	p.Thr549Ile	missense_variant	11/11		XP_006712902.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL1RL1	ENST00000233954.6	c.1646C>T	p.Thr549Ile	missense_variant	11/11	1	NM_016232.5	ENSP00000233954	P1
IL18R1	ENST00000410040.5	c.-28-10737C>T		intron_variant		2		ENSP00000386663

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

GnomAD3 exomes AF: 0.340 AC: 84564 AN: 248718 Hom.: 16987 AF XY: 0.332 AC XY: 44756 AN XY: 134948

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 SAS exome AF: 0.179

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

Gnomad4 AFR exome AF: 0.714

Gnomad4 AMR exome AF: 0.230

Gnomad4 ASJ exome AF: 0.469

Gnomad4 EAS exome AF: 0.150

Gnomad4 SAS exome AF: 0.183

Gnomad4 FIN exome AF: 0.414

Gnomad4 NFE exome AF: 0.381

Gnomad4 OTH exome AF: 0.371

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

Gnomad4 AFR AF: 0.701

Gnomad4 AMR AF: 0.318

Gnomad4 ASJ AF: 0.477

Gnomad4 EAS AF: 0.128

Gnomad4 SAS AF: 0.200

Gnomad4 FIN AF: 0.420

Gnomad4 NFE AF: 0.377

Gnomad4 OTH AF: 0.410

Alfa AF: 0.381 Hom.: 28608

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 v4.3

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
MutationTaster	Benign	1.0	P;P
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

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: rs10192157; hg19: chr2-102968356; COSMIC: COSV52112934; COSMIC: COSV52112934;