rs4321386

Variant names:

• chr2-101996551-C-G
• rs4321386
• NM_004633.4:c.-62+4540C>G

Variant summary

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

The NM_004633.4(IL1R2):​c.-62+4540C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 133,396 control chromosomes in the GnomAD database, including 1,136 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 0.12 (1136 hom., cov: 23)
• Consequence: IL1R2 NM_004633.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.108
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1R2	NM_004633.4	c.-62+4540C>G		intron_variant	Intron 1 of 8	ENST00000332549.8	NP_004624.1
IL1R2	NM_001261419.2	c.-62+4540C>G		intron_variant	Intron 1 of 6		NP_001248348.1
IL1R2	XM_006712736.4	c.14+4518C>G		intron_variant	Intron 1 of 8		XP_006712799.1
IL1R2	XM_006712734.4	c.-62+4555C>G		intron_variant	Intron 1 of 8		XP_006712797.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1R2	ENST00000332549.8	c.-62+4540C>G		intron_variant	Intron 1 of 8	1	NM_004633.4	ENSP00000330959.3
IL1R2	ENST00000464994.5	n.74+4518C>G		intron_variant	Intron 1 of 2	3
IL1R2	ENST00000493749.1	n.52+4540C>G		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes AF: 0.123 AC: 16407 AN: 133340 Hom.: 1135 Cov.: 23

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.0957

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.123 AC: 16413 AN: 133396 Hom.: 1136 Cov.: 23 AF XY: 0.130 AC XY: 8216 AN XY: 63296

African (AFR) AF: 0.102 AC: 3496 AN: 34374

American (AMR) AF: 0.156 AC: 1860 AN: 11932

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 390 AN: 3372

East Asian (EAS) AF: 0.305 AC: 1362 AN: 4462

South Asian (SAS) AF: 0.225 AC: 923 AN: 4096

European-Finnish (FIN) AF: 0.170 AC: 1185 AN: 6980

Middle Eastern (MID) AF: 0.154 AC: 32 AN: 208

European-Non Finnish (NFE) AF: 0.105 AC: 6872 AN: 65322

Other (OTH) AF: 0.118 AC: 208 AN: 1762

Alfa AF: 0.109 Hom.: 121

Bravo AF: 0.115

Asia WGS AF: 0.265 AC: 919 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.7
DANN	Benign	0.64
PhyloP100		0.11
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: rs4321386; hg19: chr2-102613013;