rs1041973

Variant names:

• chr2-102339008-C-A
• rs1041973
• NM_016232.5:c.233C>A

Variant summary

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

The NM_016232.5(IL1RL1):​c.233C>A​(p.Ala78Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 1,612,426 control chromosomes in the GnomAD database, including 49,736 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 0.30 (7901 hom., cov: 32)
  • Exomes 𝑓: 0.23 (41835 hom.)
• Consequence: IL1RL1 NM_016232.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.266
• Publications: 94 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=1.5735626E-4).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1RL1	NM_016232.5	c.233C>A	p.Ala78Glu	missense_variant	Exon 3 of 11	ENST00000233954.6	NP_057316.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1RL1	ENST00000233954.6	c.233C>A	p.Ala78Glu	missense_variant	Exon 3 of 11	1	NM_016232.5	ENSP00000233954.1

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45449 AN: 151902 Hom.: 7889 Cov.: 32

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.315

GnomAD2 exomes AF: 0.226 AC: 56625 AN: 250938 AF XY: 0.224

Gnomad AFR exome AF: 0.483

Gnomad AMR exome AF: 0.154

Gnomad ASJ exome AF: 0.373

Gnomad EAS exome AF: 0.122

Gnomad FIN exome AF: 0.210

Gnomad NFE exome AF: 0.236

Gnomad OTH exome AF: 0.256

GnomAD4 exome AF: 0.230 AC: 335974 AN: 1460406 Hom.: 41835 Cov.: 32 AF XY: 0.229 AC XY: 166080 AN XY: 726614

African (AFR) AF: 0.491 AC: 16419 AN: 33434

American (AMR) AF: 0.165 AC: 7376 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.375 AC: 9802 AN: 26116

East Asian (EAS) AF: 0.156 AC: 6171 AN: 39664

South Asian (SAS) AF: 0.152 AC: 13146 AN: 86242

European-Finnish (FIN) AF: 0.208 AC: 11137 AN: 53416

Middle Eastern (MID) AF: 0.437 AC: 2521 AN: 5764

European-Non Finnish (NFE) AF: 0.229 AC: 253981 AN: 1110732

Other (OTH) AF: 0.256 AC: 15421 AN: 60336

GnomAD4 genome AF: 0.299 AC: 45507 AN: 152020 Hom.: 7901 Cov.: 32 AF XY: 0.295 AC XY: 21935 AN XY: 74304

African (AFR) AF: 0.479 AC: 19833 AN: 41430

American (AMR) AF: 0.233 AC: 3556 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 1277 AN: 3468

East Asian (EAS) AF: 0.136 AC: 704 AN: 5174

South Asian (SAS) AF: 0.153 AC: 737 AN: 4832

European-Finnish (FIN) AF: 0.214 AC: 2260 AN: 10584

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.237 AC: 16121 AN: 67960

Other (OTH) AF: 0.314 AC: 663 AN: 2112

Alfa AF: 0.254 Hom.: 19793

Bravo AF: 0.308

TwinsUK AF: 0.221 AC: 818

ALSPAC AF: 0.226 AC: 870

ESP6500AA AF: 0.469 AC: 2066

ESP6500EA AF: 0.253 AC: 2178

ExAC AF: 0.230 AC: 27942

Asia WGS AF: 0.171 AC: 594 AN: 3478

EpiCase AF: 0.255

EpiControl AF: 0.267

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	3.8
DANN	Benign	0.81
DEOGEN2	Benign	0.048	T;.;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.082	T;T;T
MetaRNN	Benign	0.00016	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.55	N;N;.
PhyloP100		0.27
PrimateAI	Benign	0.23	T
PROVEAN	Benign	0.79	N;N;N
REVEL	Benign	0.054
Sift	Benign	0.20	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.038
MPC		0.010
ClinPred		0.0038	T
GERP RS		2.3
Varity_R		0.082
gMVP		0.30
Mutation Taster		=300/0	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: rs1041973; hg19: chr2-102955468; COSMIC: COSV52114391; COSMIC: COSV52114391;