2-102164825-A-T

Variant names:

• chr2-102164825-A-T
• NM_000877.4:c.113A>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000877.4(IL1R1):​c.113A>T​(p.Glu38Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: IL1R1 NM_000877.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.21
• Publications: 0 publications found

Genes affected

IL1R1 (HGNC:5993): (interleukin 1 receptor type 1) This gene encodes a cytokine receptor that belongs to the interleukin-1 receptor family. The encoded protein is a receptor for interleukin-1 alpha, interleukin-1 beta, and interleukin-1 receptor antagonist. It is an important mediator involved in many cytokine-induced immune and inflammatory responses. This gene is located in a cluster of related cytokine receptor genes on chromosome 2q12. [provided by RefSeq, Dec 2013]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1R1	NM_000877.4	c.113A>T	p.Glu38Val	missense_variant	Exon 4 of 12	ENST00000410023.6	NP_000868.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1R1	ENST00000410023.6	c.113A>T	p.Glu38Val	missense_variant	Exon 4 of 12	1	NM_000877.4	ENSP00000386380.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 06, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.113A>T (p.E38V) alteration is located in exon 3 (coding exon 2) of the IL1R1 gene. This alteration results from a A to T substitution at nucleotide position 113, causing the glutamic acid (E) at amino acid position 38 to be replaced by a valine (V). 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	Pathogenic	0.83
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T;T;.;T;.;.;T;.;T;.
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.84	T;T;.;T;.;T;T;T;T;T
M_CAP	Benign	0.054	D
MetaRNN	Uncertain	0.64	D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.90	T
MutationAssessor	Pathogenic	3.3	.;.;.;.;.;.;.;.;M;.
PhyloP100		5.2
PrimateAI	Benign	0.44	T
PROVEAN	Pathogenic	-7.0	D;N;N;D;N;D;D;N;D;D
REVEL	Benign	0.23
Sift	Pathogenic	0.0	D;D;D;D;D;D;D;D;D;D
Sift4G	Pathogenic	0.0	D;T;D;D;D;D;D;D;T;D
Polyphen		0.80, 1.0, 1.0	.;P;D;.;D;.;.;D;D;.
Vest4		0.53, 0.45, 0.55, 0.45, 0.53, 0.50
MutPred		0.58		Loss of disorder (P = 0.05);Loss of disorder (P = 0.05);Loss of disorder (P = 0.05);Loss of disorder (P = 0.05);Loss of disorder (P = 0.05);Loss of disorder (P = 0.05);Loss of disorder (P = 0.05);Loss of disorder (P = 0.05);Loss of disorder (P = 0.05);Loss of disorder (P = 0.05);
MVP		0.59
MPC		0.96
ClinPred		0.99	D
GERP RS		5.4
Varity_R		0.62
gMVP		0.79
Mutation Taster		=76/24	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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

hg19: chr2-102781285;