2-102340207-A-C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016232.5(IL1RL1):​c.382A>C​(p.Asn128His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N128K) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

IL1RL1
NM_016232.5 missense

Scores

1
5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.241

Publications

0 publications found
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2623384).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IL1RL1NM_016232.5 linkc.382A>C p.Asn128His missense_variant Exon 4 of 11 ENST00000233954.6 NP_057316.3 Q01638-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IL1RL1ENST00000233954.6 linkc.382A>C p.Asn128His missense_variant Exon 4 of 11 1 NM_016232.5 ENSP00000233954.1 Q01638-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
May 17, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.382A>C (p.N128H) alteration is located in exon 4 (coding exon 3) of the IL1RL1 gene. This alteration results from a A to C substitution at nucleotide position 382, causing the asparagine (N) at amino acid position 128 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.17
BayesDel_addAF
Benign
-0.081
T
BayesDel_noAF
Benign
-0.35
CADD
Benign
17
DANN
Uncertain
0.99
DEOGEN2
Benign
0.17
.;T;.;T
Eigen
Benign
-0.20
Eigen_PC
Benign
-0.44
FATHMM_MKL
Benign
0.059
N
LIST_S2
Benign
0.67
T;T;T;T
M_CAP
Benign
0.050
D
MetaRNN
Benign
0.26
T;T;T;T
MetaSVM
Benign
-0.49
T
MutationAssessor
Uncertain
2.7
.;M;M;.
PhyloP100
0.24
PrimateAI
Uncertain
0.48
T
PROVEAN
Uncertain
-2.8
D;D;D;D
REVEL
Benign
0.26
Sift
Uncertain
0.023
D;D;D;D
Sift4G
Pathogenic
0.0
D;T;D;D
Polyphen
1.0, 1.0
.;D;D;.
Vest4
0.40
MutPred
0.30
.;Gain of sheet (P = 0.039);Gain of sheet (P = 0.039);Gain of sheet (P = 0.039);
MVP
0.89
MPC
0.067
ClinPred
0.85
D
GERP RS
-2.3
Varity_R
0.13
gMVP
0.54
Mutation Taster
=89/11
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

hg19: chr2-102956667; API