rs3218977

Positions:

• chr2-102024739-A-G

Variant summary

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

The NM_001261419.2(IL1R2):​c.*67A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 1,592,236 control chromosomes in the GnomAD database, including 19,659 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 0.15 (1825 hom., cov: 32)
  • Exomes 𝑓: 0.15 (17834 hom.)
• Consequence: IL1R2 NM_001261419.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.951

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL1R2	NM_004633.4	c.887+71A>G		intron_variant		ENST00000332549.8	NP_004624.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL1R2	ENST00000332549.8	c.887+71A>G		intron_variant		1	NM_004633.4	ENSP00000330959.3

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22444 AN: 152104 Hom.: 1818 Cov.: 32

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.251

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.0977

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.155

GnomAD4 exome AF: 0.153 AC: 220070 AN: 1440014 Hom.: 17834 Cov.: 28 AF XY: 0.156 AC XY: 111778 AN XY: 715246

Gnomad4 AFR exome AF: 0.135

Gnomad4 AMR exome AF: 0.139

Gnomad4 ASJ exome AF: 0.126

Gnomad4 EAS exome AF: 0.219

Gnomad4 SAS exome AF: 0.266

Gnomad4 FIN exome AF: 0.0995

Gnomad4 NFE exome AF: 0.146

Gnomad4 OTH exome AF: 0.159

GnomAD4 genome AF: 0.148 AC: 22467 AN: 152222 Hom.: 1825 Cov.: 32 AF XY: 0.150 AC XY: 11138 AN XY: 74424

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.134

Gnomad4 EAS AF: 0.251

Gnomad4 SAS AF: 0.274

Gnomad4 FIN AF: 0.0977

Gnomad4 NFE AF: 0.139

Gnomad4 OTH AF: 0.163

Alfa AF: 0.145 Hom.: 3450

Bravo AF: 0.148

Asia WGS AF: 0.255 AC: 888 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.27
DANN	Benign	0.51

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: rs3218977; hg19: chr2-102641201; COSMIC: COSV60207303; COSMIC: COSV60207303;