2-102351752-A-G

Position:

• chr2-102351752-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016232.5(IL1RL1):​c.1502A>G​(p.Gln501Arg) 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 1,612,806 control chromosomes in the GnomAD database, including 122,646 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q501K) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.45 (17654 hom., cov: 30)
  • Exomes 𝑓: 0.37 (104992 hom.)
• Consequence: IL1RL1 NM_016232.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.111

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=1.002102E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1RL1	NM_016232.5	c.1502A>G	p.Gln501Arg	missense_variant	11/11	ENST00000233954.6
IL1RL1	XM_006712839.4	c.1502A>G	p.Gln501Arg	missense_variant	11/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1RL1	ENST00000233954.6	c.1502A>G	p.Gln501Arg	missense_variant	11/11	1	NM_016232.5	P1
IL18R1	ENST00000410040.5	c.-28-10881A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68387 AN: 151676 Hom.: 17625 Cov.: 30

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: 0.200

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.248

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.414

GnomAD3 exomes AF: 0.341 AC: 85563 AN: 250992 Hom.: 17231 AF XY: 0.332 AC XY: 44979 AN XY: 135650

Gnomad AFR exome AF: 0.710

Gnomad AMR exome AF: 0.218

Gnomad ASJ exome AF: 0.462

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: 538251 AN: 1461012 Hom.: 104992 Cov.: 37 AF XY: 0.362 AC XY: 263132 AN XY: 726854

Gnomad4 AFR exome AF: 0.714

Gnomad4 AMR exome AF: 0.230

Gnomad4 ASJ exome AF: 0.469

Gnomad4 EAS exome AF: 0.151

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: 151794 Hom.: 17654 Cov.: 30 AF XY: 0.444 AC XY: 32954 AN XY: 74220

Gnomad4 AFR AF: 0.701

Gnomad4 AMR AF: 0.317

Gnomad4 ASJ AF: 0.477

Gnomad4 EAS AF: 0.128

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.421

Gnomad4 NFE AF: 0.377

Gnomad4 OTH AF: 0.410

Alfa AF: 0.397 Hom.: 11937

Bravo AF: 0.457

TwinsUK AF: 0.377 AC: 1398

ALSPAC AF: 0.373 AC: 1436

ESP6500AA AF: 0.0999 AC: 440

ESP6500EA AF: 0.0276 AC: 237

ExAC AF: 0.349 AC: 42335

Asia WGS AF: 0.180 AC: 627 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	0.061
BayesDel_addAF	Benign	-0.85	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.10
DANN	Benign	0.44
DEOGEN2	Benign	0.030	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.24	T
MetaRNN	Benign	0.0000010	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.43	N
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.22	T
PROVEAN	Benign	0.99	N
REVEL	Benign	0.028
Sift	Benign	0.66	T
Sift4G	Benign	0.73	T
Polyphen		0.0	B
Vest4		0.0090
MPC		0.010
ClinPred		0.0046	T
GERP RS		-0.57
Varity_R		0.026
gMVP		0.15

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: rs10204137; hg19: chr2-102968212; COSMIC: COSV52113213; COSMIC: COSV52113213;