rs11674595

Positions:

• chr2-101994530-T-C
• chr2-101994530-T-G

Variant summary

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

The NM_004633.4(IL1R2):​c.-62+2519T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 152,184 control chromosomes in the GnomAD database, including 4,750 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 0.22 (4750 hom., cov: 32)
• Consequence: IL1R2 NM_004633.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.285

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1R2	NM_004633.4	c.-62+2519T>C		intron_variant		ENST00000332549.8
IL1R2	NM_001261419.2	c.-62+2519T>C		intron_variant
IL1R2	XM_006712734.4	c.-62+2534T>C		intron_variant
IL1R2	XM_006712736.4	c.14+2497T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1R2	ENST00000332549.8	c.-62+2519T>C		intron_variant		1	NM_004633.4	P1
IL1R2	ENST00000464994.5	n.74+2497T>C		intron_variant, non_coding_transcript_variant		3
IL1R2	ENST00000493749.1	n.52+2519T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34183 AN: 152066 Hom.: 4744 Cov.: 32

Gnomad AFR AF: 0.0794

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.237

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

GnomAD4 genome AF: 0.225 AC: 34196 AN: 152184 Hom.: 4750 Cov.: 32 AF XY: 0.231 AC XY: 17194 AN XY: 74394

Gnomad4 AFR AF: 0.0793

Gnomad4 AMR AF: 0.269

Gnomad4 ASJ AF: 0.189

Gnomad4 EAS AF: 0.255

Gnomad4 SAS AF: 0.120

Gnomad4 FIN AF: 0.450

Gnomad4 NFE AF: 0.275

Gnomad4 OTH AF: 0.233

Alfa AF: 0.248 Hom.: 787

Bravo AF: 0.210

Asia WGS AF: 0.158 AC: 551 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11674595; hg19: chr2-102610992; COSMIC: COSV60206292; COSMIC: COSV60206292;