NM_004633.4:c.-61-191C>T

Variant names:

• chr2-102008324-C-T
• rs2302589
• NM_004633.4:c.-61-191C>T

Variant summary

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

The NM_004633.4(IL1R2):​c.-61-191C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,188 control chromosomes in the GnomAD database, including 2,580 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 (2580 hom., cov: 32)
• Consequence: IL1R2 NM_004633.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.204
• Publications: 8 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1R2	NM_004633.4	c.-61-191C>T		intron_variant	Intron 1 of 8	ENST00000332549.8	NP_004624.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1R2	ENST00000332549.8	c.-61-191C>T		intron_variant	Intron 1 of 8	1	NM_004633.4	ENSP00000330959.3

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25428 AN: 152070 Hom.: 2573 Cov.: 32

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.167 AC: 25468 AN: 152188 Hom.: 2580 Cov.: 32 AF XY: 0.171 AC XY: 12740 AN XY: 74384

African (AFR) AF: 0.254 AC: 10548 AN: 41514

American (AMR) AF: 0.155 AC: 2366 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 408 AN: 3472

East Asian (EAS) AF: 0.323 AC: 1668 AN: 5170

South Asian (SAS) AF: 0.214 AC: 1033 AN: 4822

European-Finnish (FIN) AF: 0.172 AC: 1816 AN: 10584

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7181 AN: 68008

Other (OTH) AF: 0.152 AC: 321 AN: 2110

Alfa AF: 0.126 Hom.: 740

Bravo AF: 0.171

Asia WGS AF: 0.302 AC: 1047 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	1.1
DANN	Benign	0.70
PhyloP100		-0.20
PromoterAI		0.017	Neutral
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: rs2302589; hg19: chr2-102624786;