rs3819370

chr2-102016112-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004633.4(IL1R2):c.513+61A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 1,323,420 control chromosomes in the GnomAD database, including 14,520 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 0.17 (2607 hom., cov: 32)
  • Exomes 𝑓: 0.13 (11913 hom.)
• Consequence: IL1R2 NM_004633.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.728

Genes affected

IL1R2 (HGNC:5994): (interleukin 1 receptor type 2) The protein encoded by this gene is a cytokine receptor that belongs to the interleukin 1 receptor family. This protein binds interleukin alpha (IL1A), interleukin beta (IL1B), and interleukin 1 receptor, type I(IL1R1/IL1RA), and acts as a decoy receptor that inhibits the activity of its ligands. Interleukin 4 (IL4) is reported to antagonize the activity of interleukin 1 by inducing the expression and release of this cytokine. This gene and three other genes form a cytokine receptor gene cluster on chromosome 2q12. Alternative splicing results in multiple transcript variants and protein isoforms. Alternative splicing produces both membrane-bound and soluble proteins. A soluble protein is also produced by proteolytic cleavage. [provided by RefSeq, May 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1R2	NM_004633.4	c.513+61A>G		intron_variant		ENST00000332549.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1R2	ENST00000332549.8	c.513+61A>G		intron_variant		1	NM_004633.4	P1

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25734 AN: 152016 Hom.: 2603 Cov.: 32

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.286

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.148

GnomAD4 exome AF: 0.128 AC: 150210 AN: 1171286 Hom.: 11913 Cov.: 14 AF XY: 0.130 AC XY: 76596 AN XY: 588628

Gnomad4 AFR exome AF: 0.271

Gnomad4 AMR exome AF: 0.181

Gnomad4 ASJ exome AF: 0.122

Gnomad4 EAS exome AF: 0.316

Gnomad4 SAS exome AF: 0.205

Gnomad4 FIN exome AF: 0.182

Gnomad4 NFE exome AF: 0.103

Gnomad4 OTH exome AF: 0.146

GnomAD4 genome AF: 0.169 AC: 25775 AN: 152134 Hom.: 2607 Cov.: 32 AF XY: 0.173 AC XY: 12893 AN XY: 74372

Gnomad4 AFR AF: 0.266

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.118

Gnomad4 EAS AF: 0.286

Gnomad4 SAS AF: 0.213

Gnomad4 FIN AF: 0.172

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.151

Alfa AF: 0.144 Hom.: 237

Bravo AF: 0.173

Asia WGS AF: 0.279 AC: 968 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	1.4
Dann	Benign	0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3819370; hg19: chr2-102632574; COSMIC: COSV60206795;