NM_000877.4:c.1366A>C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_000877.4(IL1R1):​c.1366A>C​(p.Arg456Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0473 in 1,614,118 control chromosomes in the GnomAD database, including 2,191 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.057 (310 hom., cov: 32)
  • Exomes 𝑓: 0.046 (1881 hom.)
• Consequence: IL1R1 NM_000877.4 synonymous
• 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP7: Synonymous conserved (PhyloP=0.101 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0839 is higher than 0.05.

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>C	p.Arg456Arg	synonymous	Exon 12 of 12	NP_000868.1
	IL1R1	NM_001320978.2		c.1366A>C	p.Arg456Arg	synonymous	Exon 12 of 12	NP_001307907.1
	IL1R1	NM_001320980.2		c.1366A>C	p.Arg456Arg	synonymous	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>C	p.Arg456Arg	synonymous	Exon 12 of 12	ENSP00000386380.1
	IL1R1	ENST00000409929.5	TSL:1	c.1273A>C	p.Arg425Arg	synonymous	Exon 12 of 12	ENSP00000386776.1
	IL1R1	ENST00000853658.1		c.1366A>C	p.Arg456Arg	synonymous	Exon 12 of 12	ENSP00000523717.1

Frequencies

GnomAD3 genomes AF: 0.0567 AC: 8634 AN: 152198 Hom.: 311 Cov.: 32

Gnomad AFR AF: 0.0863

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.0610

Gnomad ASJ AF: 0.0657

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0116

Gnomad FIN AF: 0.0185

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.0484

Gnomad OTH AF: 0.0712

GnomAD2 exomes AF: 0.0416 AC: 10443 AN: 251320 AF XY: 0.0404

Gnomad AFR exome AF: 0.0881

Gnomad AMR exome AF: 0.0434

Gnomad ASJ exome AF: 0.0680

Gnomad EAS exome AF: 0.000435

Gnomad FIN exome AF: 0.0144

Gnomad NFE exome AF: 0.0506

Gnomad OTH exome AF: 0.0566

GnomAD4 exome AF: 0.0463 AC: 67736 AN: 1461800 Hom.: 1881 Cov.: 32 AF XY: 0.0455 AC XY: 33078 AN XY: 727198

African (AFR) AF: 0.0864 AC: 2894 AN: 33476

American (AMR) AF: 0.0471 AC: 2108 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0679 AC: 1775 AN: 26134

East Asian (EAS) AF: 0.000176 AC: 7 AN: 39694

South Asian (SAS) AF: 0.0138 AC: 1191 AN: 86256

European-Finnish (FIN) AF: 0.0144 AC: 769 AN: 53418

Middle Eastern (MID) AF: 0.146 AC: 840 AN: 5768

European-Non Finnish (NFE) AF: 0.0494 AC: 54979 AN: 1111938

Other (OTH) AF: 0.0525 AC: 3173 AN: 60392

GnomAD4 genome AF: 0.0567 AC: 8642 AN: 152318 Hom.: 310 Cov.: 32 AF XY: 0.0552 AC XY: 4114 AN XY: 74488

African (AFR) AF: 0.0863 AC: 3586 AN: 41570

American (AMR) AF: 0.0609 AC: 932 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0657 AC: 228 AN: 3470

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5188

South Asian (SAS) AF: 0.0118 AC: 57 AN: 4826

European-Finnish (FIN) AF: 0.0185 AC: 197 AN: 10624

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.0484 AC: 3294 AN: 68016

Other (OTH) AF: 0.0704 AC: 149 AN: 2116

Alfa AF: 0.0564 Hom.: 446

Bravo AF: 0.0638

Asia WGS AF: 0.0130 AC: 46 AN: 3478

EpiCase AF: 0.0588

EpiControl AF: 0.0596

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.6
DANN	Benign	0.72
PhyloP100		0.10
Mutation Taster		=100/0	polymorphism (auto)

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;