NM_000877.4:c.1540C>A

Variant names:

• chr2-102176589-C-A
• rs201410299
• NM_000877.4:c.1540C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000877.4(IL1R1):​c.1540C>A​(p.Arg514Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict 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. R514C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: IL1R1 NM_000877.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.147
• 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]

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39452022).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1R1	NM_000877.4	c.1540C>A	p.Arg514Ser	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.1540C>A	p.Arg514Ser	missense_variant	Exon 12 of 12	1	NM_000877.4	ENSP00000386380.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461874 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727236

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111998

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0092	T;T
Eigen	Benign	-0.066
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.16	N
LIST_S2	Uncertain	0.95	D;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.39	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.8	.;M
PhyloP100		-0.15
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-3.8	D;D
REVEL	Benign	0.17
Sift	Benign	0.041	D;D
Sift4G	Uncertain	0.051	T;D
Polyphen		0.98	D;P
Vest4		0.51
MutPred		0.69		.;Loss of MoRF binding (P = 0.0067);
MVP		0.30
MPC		0.93
ClinPred		0.96	D
GERP RS		2.8
Varity_R		0.34
gMVP		0.30
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs201410299; hg19: chr2-102793049;