2-102340190-T-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.365T>C​(p.Val122Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,451,098 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

IL1RL1
NM_016232.5 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.145

Publications

2 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=0.08649671).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IL1RL1NM_016232.5 linkc.365T>C p.Val122Ala 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.365T>C p.Val122Ala missense_variant Exon 4 of 11 1 NM_016232.5 ENSP00000233954.1 Q01638-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD2 exomes
AF:
0.00000823
AC:
2
AN:
242980
AF XY:
0.0000152
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000112
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000207
AC:
3
AN:
1451098
Hom.:
0
Cov.:
29
AF XY:
0.00000416
AC XY:
3
AN XY:
721912
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33026
American (AMR)
AF:
0.00
AC:
0
AN:
41868
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25980
East Asian (EAS)
AF:
0.0000508
AC:
2
AN:
39394
South Asian (SAS)
AF:
0.00
AC:
0
AN:
84484
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53358
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5736
European-Non Finnish (NFE)
AF:
9.03e-7
AC:
1
AN:
1107252
Other (OTH)
AF:
0.00
AC:
0
AN:
60000
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.492
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
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 07, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.365T>C (p.V122A) alteration is located in exon 4 (coding exon 3) of the IL1RL1 gene. This alteration results from a T to C substitution at nucleotide position 365, causing the valine (V) at amino acid position 122 to be replaced by an alanine (A). 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
0.13
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.39
CADD
Benign
14
DANN
Benign
0.90
DEOGEN2
Benign
0.074
.;T;.;T
Eigen
Benign
-0.82
Eigen_PC
Benign
-0.86
FATHMM_MKL
Benign
0.028
N
LIST_S2
Benign
0.51
T;T;T;T
M_CAP
Benign
0.028
D
MetaRNN
Benign
0.086
T;T;T;T
MetaSVM
Benign
-0.92
T
MutationAssessor
Uncertain
2.2
.;M;M;.
PhyloP100
0.14
PrimateAI
Benign
0.33
T
PROVEAN
Benign
-1.1
N;N;N;N
REVEL
Benign
0.096
Sift
Benign
0.063
T;T;T;T
Sift4G
Benign
0.19
T;T;T;T
Polyphen
0.32, 0.45
.;B;B;.
Vest4
0.10
MutPred
0.55
.;Gain of disorder (P = 0.0555);Gain of disorder (P = 0.0555);Gain of disorder (P = 0.0555);
MVP
0.72
MPC
0.016
ClinPred
0.94
D
GERP RS
1.6
Varity_R
0.21
gMVP
0.37
Mutation Taster
=76/24
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
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

dbSNP: rs1475246537; hg19: chr2-102956650; API