rs3218974

Variant names:

• chr2-102024409-A-G
• rs3218974
• NM_004633.4:c.752-124A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-102024409-A-G
• chr2-102024409-A-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.752-124A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 695,656 control chromosomes in the GnomAD database, including 27,249 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 0.27 (5911 hom., cov: 32)
  • Exomes 𝑓: 0.27 (21338 hom.)
• Consequence: IL1R2 NM_004633.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.377
• Publications: 5 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1R2	NM_004633.4	c.752-124A>G		intron_variant	Intron 6 of 8	ENST00000332549.8	NP_004624.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1R2	ENST00000332549.8	c.752-124A>G		intron_variant	Intron 6 of 8	1	NM_004633.4	ENSP00000330959.3

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41413 AN: 151902 Hom.: 5900 Cov.: 32

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.266

GnomAD4 exome AF: 0.273 AC: 148458 AN: 543638 Hom.: 21338 AF XY: 0.267 AC XY: 77217 AN XY: 289474

African (AFR) AF: 0.260 AC: 3886 AN: 14974

American (AMR) AF: 0.336 AC: 9160 AN: 27230

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 3245 AN: 15364

East Asian (EAS) AF: 0.298 AC: 10340 AN: 34706

South Asian (SAS) AF: 0.178 AC: 9725 AN: 54606

European-Finnish (FIN) AF: 0.407 AC: 19931 AN: 48968

Middle Eastern (MID) AF: 0.226 AC: 650 AN: 2878

European-Non Finnish (NFE) AF: 0.266 AC: 83936 AN: 315676

Other (OTH) AF: 0.259 AC: 7585 AN: 29236

GnomAD4 genome AF: 0.273 AC: 41462 AN: 152018 Hom.: 5911 Cov.: 32 AF XY: 0.277 AC XY: 20583 AN XY: 74292

African (AFR) AF: 0.252 AC: 10456 AN: 41450

American (AMR) AF: 0.292 AC: 4467 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 778 AN: 3472

East Asian (EAS) AF: 0.264 AC: 1365 AN: 5168

South Asian (SAS) AF: 0.180 AC: 869 AN: 4822

European-Finnish (FIN) AF: 0.417 AC: 4395 AN: 10552

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.269 AC: 18296 AN: 67970

Other (OTH) AF: 0.264 AC: 557 AN: 2110

Alfa AF: 0.282 Hom.: 909

Bravo AF: 0.266

Asia WGS AF: 0.233 AC: 813 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.4
DANN	Benign	0.50
PhyloP100		-0.38
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: rs3218974; hg19: chr2-102640871;