2-102176415-A-G

Variant names:

• chr2-102176415-A-G
• rs3917320
• NM_000877.4:c.1366A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000877.4(IL1R1):​c.1366A>G​(p.Arg456Gly) 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 1,461,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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: 0.101
• Publications: 20 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.067195565).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000877.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1R1	NM_000877.4	MANE Select	c.1366A>G	p.Arg456Gly	missense	Exon 12 of 12	NP_000868.1
	IL1R1	NM_001320978.2		c.1366A>G	p.Arg456Gly	missense	Exon 12 of 12	NP_001307907.1
	IL1R1	NM_001320980.2		c.1366A>G	p.Arg456Gly	missense	Exon 12 of 12	NP_001307909.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1R1	ENST00000410023.6	TSL:1 MANE Select	c.1366A>G	p.Arg456Gly	missense	Exon 12 of 12	ENSP00000386380.1
	IL1R1	ENST00000409929.5	TSL:1	c.1273A>G	p.Arg425Gly	missense	Exon 12 of 12	ENSP00000386776.1
	IL1R1	ENST00000853658.1		c.1366A>G	p.Arg456Gly	missense	Exon 12 of 12	ENSP00000523717.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000796 AC: 2 AN: 251320 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461856 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727230

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: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

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

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111984

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

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	13
DANN	Benign	0.73
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.051	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.067	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.10
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.94	N
REVEL	Benign	0.054
Sift	Benign	0.58	T
Sift4G	Benign	0.50	T
Polyphen		0.0010	B
Vest4		0.32
MutPred		0.58		Loss of MoRF binding (P = 0.0053)
MVP		0.20
MPC		0.32
ClinPred		0.015	T
GERP RS		-1.0
Varity_R		0.062
gMVP		0.34
Mutation Taster		=96/4	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: rs3917320; hg19: chr2-102792875;