rs7570441

Variant names:

• chr2-102000533-G-A
• rs7570441
• NM_004633.4:c.-61-7982G>A

Variant summary

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

The NM_004633.4(IL1R2):​c.-61-7982G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 152,080 control chromosomes in the GnomAD database, including 14,765 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 0.44 (14765 hom., cov: 33)
• Consequence: IL1R2 NM_004633.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0340
• Publications: 15 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 (AFR) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1R2	NM_004633.4	c.-61-7982G>A		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.-61-7982G>A		intron_variant	Intron 1 of 8	1	NM_004633.4	ENSP00000330959.3
IL1R2	ENST00000393414.6	c.-62+1417G>A		intron_variant	Intron 1 of 8	1		ENSP00000377066.2
IL1R2	ENST00000464994.5	n.75-7982G>A		intron_variant	Intron 1 of 2	3
IL1R2	ENST00000493749.1	n.53-7982G>A		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66600 AN: 151960 Hom.: 14749 Cov.: 33

Gnomad AFR AF: 0.465

Gnomad AMI AF: 0.372

Gnomad AMR AF: 0.454

Gnomad ASJ AF: 0.357

Gnomad EAS AF: 0.465

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.559

Gnomad MID AF: 0.334

Gnomad NFE AF: 0.404

Gnomad OTH AF: 0.429

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

GnomAD4 genome AF: 0.438 AC: 66666 AN: 152080 Hom.: 14765 Cov.: 33 AF XY: 0.446 AC XY: 33127 AN XY: 74348

African (AFR) AF: 0.465 AC: 19302 AN: 41490

American (AMR) AF: 0.454 AC: 6944 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.357 AC: 1239 AN: 3470

East Asian (EAS) AF: 0.465 AC: 2398 AN: 5160

South Asian (SAS) AF: 0.430 AC: 2074 AN: 4818

European-Finnish (FIN) AF: 0.559 AC: 5912 AN: 10570

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.404 AC: 27441 AN: 67970

Other (OTH) AF: 0.432 AC: 912 AN: 2112

Alfa AF: 0.415 Hom.: 6637

Bravo AF: 0.433

Asia WGS AF: 0.462 AC: 1611 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	1.5
DANN	Benign	0.67
PhyloP100		-0.034
Mutation Taster		=99/1	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: rs7570441; hg19: chr2-102616995; COSMIC: COSV60206331; COSMIC: COSV60206331;