2-102176590-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000877.4(IL1R1):c.1541G>T(p.Arg514Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. R514C) has been classified 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: 2.34

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]

IL1R1-AS1 (HGNC:53898): (IL1R1 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1R1	NM_000877.4	c.1541G>T	p.Arg514Leu	missense_variant	12/12	ENST00000410023.6
IL1R1-AS1	NR_174960.1	n.305+3322C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1R1	ENST00000410023.6	c.1541G>T	p.Arg514Leu	missense_variant	12/12	1	NM_000877.4	P1
IL1R1-AS1	ENST00000428188.1	n.305+3322C>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 06, 2023

The c.1541G>T (p.R514L) alteration is located in exon 11 (coding exon 10) of the IL1R1 gene. This alteration results from a G to T substitution at nucleotide position 1541, causing the arginine (R) at amino acid position 514 to be replaced by a leucine (L). 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	0.14
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
Cadd	Uncertain	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.012	T;T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.86	D;T
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.61	D;D
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;D;N;N;N
PrimateAI	Benign	0.31	T
PROVEAN	Pathogenic	-5.0	D;D
REVEL	Benign	0.22
Sift	Benign	0.038	D;D
Sift4G	Uncertain	0.037	D;D
Polyphen		0.98	D;P
Vest4		0.65
MutPred		0.68		.;Loss of MoRF binding (P = 8e-04);
MVP		0.37
MPC		0.96
ClinPred		0.98	D
GERP RS		4.7
Varity_R		0.26
gMVP		0.38

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-102793050;