rs3917320

Positions:

• chr2-102176415-A-C
• chr2-102176415-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_000877.4(IL1R1):​c.1366A>C​(p.Arg456=) 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

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 Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL1R1	NM_000877.4	c.1366A>C	p.Arg456=	synonymous_variant	12/12	ENST00000410023.6	NP_000868.1
IL1R1-AS1	NR_174960.1	n.305+3497T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL1R1	ENST00000410023.6	c.1366A>C	p.Arg456=	synonymous_variant	12/12	1	NM_000877.4	ENSP00000386380	P1
IL1R1-AS1	ENST00000428188.1	n.305+3497T>G		intron_variant, non_coding_transcript_variant		3

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

GnomAD3 exomes AF: 0.0416 AC: 10443 AN: 251320 Hom.: 340 AF XY: 0.0404 AC XY: 5494 AN XY: 135846

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 SAS exome AF: 0.0135

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

Gnomad4 AFR exome AF: 0.0864

Gnomad4 AMR exome AF: 0.0471

Gnomad4 ASJ exome AF: 0.0679

Gnomad4 EAS exome AF: 0.000176

Gnomad4 SAS exome AF: 0.0138

Gnomad4 FIN exome AF: 0.0144

Gnomad4 NFE exome AF: 0.0494

Gnomad4 OTH exome AF: 0.0525

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

Gnomad4 AFR AF: 0.0863

Gnomad4 AMR AF: 0.0609

Gnomad4 ASJ AF: 0.0657

Gnomad4 EAS AF: 0.000771

Gnomad4 SAS AF: 0.0118

Gnomad4 FIN AF: 0.0185

Gnomad4 NFE AF: 0.0484

Gnomad4 OTH AF: 0.0704

Alfa AF: 0.0556 Hom.: 347

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.6
DANN	Benign	0.72

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

LitVar

Other links and lift over

dbSNP: rs3917320; hg19: chr2-102792875;