NM_000877.4:c.1442A>G

Variant names:

• chr2-102176491-A-G
• rs148364799
• NM_000877.4:c.1442A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000877.4(IL1R1):​c.1442A>G​(p.Asp481Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D481A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IL1R1 NM_000877.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.05
• Publications: 5 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]

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

ACMG classification

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=0.2081129).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1R1	NM_000877.4	c.1442A>G	p.Asp481Gly	missense_variant	Exon 12 of 12	ENST00000410023.6	NP_000868.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1R1	ENST00000410023.6	c.1442A>G	p.Asp481Gly	missense_variant	Exon 12 of 12	1	NM_000877.4	ENSP00000386380.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.017	T;T
Eigen	Benign	-0.12
Eigen_PC	Benign	0.0075
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.94	D;T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	.;L
PhyloP100		5.0
PrimateAI	Benign	0.35	T
PROVEAN	Pathogenic	-5.8	D;D
REVEL	Benign	0.15
Sift	Uncertain	0.0040	D;D
Sift4G	Uncertain	0.014	D;D
Polyphen		0.54	P;B
Vest4		0.32
MutPred		0.61		.;Gain of ubiquitination at K484 (P = 0.1008);
MVP		0.34
MPC		0.86
ClinPred		0.97	D
GERP RS		4.4
Varity_R		0.57
gMVP		0.34
Mutation Taster		=76/24	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs148364799; hg19: chr2-102792951;