rs3218977

Variant names:

• chr2-102024739-A-G
• rs3218977
• ENST00000441002.1:c.*67A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000441002.1(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 ENST00000441002.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.951
• Publications: 25 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000441002.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1R2	NM_004633.4	MANE Select	c.887+71A>G		intron	N/A	NP_004624.1
	IL1R2	NM_001261419.2		c.*67A>G		3_prime_UTR	Exon 7 of 7	NP_001248348.1
	IL1R2	NR_048564.2		n.1104+71A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1R2	ENST00000441002.1	TSL:1	c.*67A>G		3_prime_UTR	Exon 6 of 6	ENSP00000414611.1
	IL1R2	ENST00000332549.8	TSL:1 MANE Select	c.887+71A>G		intron	N/A	ENSP00000330959.3
	IL1R2	ENST00000393414.6	TSL:1	c.887+71A>G		intron	N/A	ENSP00000377066.2

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

African (AFR) AF: 0.135 AC: 4443 AN: 32850

American (AMR) AF: 0.139 AC: 5957 AN: 42734

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 3201 AN: 25466

East Asian (EAS) AF: 0.219 AC: 8595 AN: 39252

South Asian (SAS) AF: 0.266 AC: 22538 AN: 84628

European-Finnish (FIN) AF: 0.0995 AC: 5262 AN: 52872

Middle Eastern (MID) AF: 0.156 AC: 869 AN: 5562

European-Non Finnish (NFE) AF: 0.146 AC: 159762 AN: 1097318

Other (OTH) AF: 0.159 AC: 9443 AN: 59332

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

African (AFR) AF: 0.144 AC: 5981 AN: 41530

American (AMR) AF: 0.156 AC: 2390 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 464 AN: 3466

East Asian (EAS) AF: 0.251 AC: 1301 AN: 5186

South Asian (SAS) AF: 0.274 AC: 1325 AN: 4830

European-Finnish (FIN) AF: 0.0977 AC: 1035 AN: 10594

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.139 AC: 9480 AN: 68018

Other (OTH) AF: 0.163 AC: 344 AN: 2110

Alfa AF: 0.143 Hom.: 7008

Bravo AF: 0.148

Asia WGS AF: 0.255 AC: 888 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.27
DANN	Benign	0.51
PhyloP100		-0.95
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: rs3218977; hg19: chr2-102641201; COSMIC: COSV60207303; COSMIC: COSV60207303;