rs3218984

Positions:

• chr2-102027999-T-C

Variant summary

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

The NM_004633.4(IL1R2):​c.1031-227T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 152,052 control chromosomes in the GnomAD database, including 5,459 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 0.26 (5459 hom., cov: 32)
• Consequence: IL1R2 NM_004633.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.07

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1R2	NM_004633.4	c.1031-227T>C		intron_variant		ENST00000332549.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1R2	ENST00000332549.8	c.1031-227T>C		intron_variant		1	NM_004633.4	P1
IL1R2	ENST00000393414.6	c.1031-227T>C		intron_variant		1		P1
IL1R2	ENST00000474085.5	n.467-227T>C		intron_variant, non_coding_transcript_variant		2
IL1R2	ENST00000485335.1	n.512-227T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39759 AN: 151932 Hom.: 5451 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.258

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.262 AC: 39800 AN: 152052 Hom.: 5459 Cov.: 32 AF XY: 0.266 AC XY: 19782 AN XY: 74316

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.290

Gnomad4 ASJ AF: 0.216

Gnomad4 EAS AF: 0.261

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.413

Gnomad4 NFE AF: 0.268

Gnomad4 OTH AF: 0.256

Alfa AF: 0.261 Hom.: 2484

Bravo AF: 0.256

Asia WGS AF: 0.197 AC: 688 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.020
DANN	Benign	0.18

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: rs3218984; hg19: chr2-102644461; COSMIC: COSV60205502; COSMIC: COSV60205502;