rs719250

Variant names:

• chr2-102007256-C-T
• rs719250
• NM_004633.4:c.-61-1259C>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.-61-1259C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,114 control chromosomes in the GnomAD database, including 1,206 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 0.11 (1206 hom., cov: 32)
• Consequence: IL1R2 NM_004633.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12
• Publications: 14 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004633.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1R2	NM_004633.4	MANE Select	c.-61-1259C>T		intron	N/A	NP_004624.1
	IL1R2	NM_001261419.2		c.-61-1259C>T		intron	N/A	NP_001248348.1
	IL1R2	NR_048564.2		n.157-1259C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1R2	ENST00000332549.8	TSL:1 MANE Select	c.-61-1259C>T		intron	N/A	ENSP00000330959.3
	IL1R2	ENST00000393414.6	TSL:1	c.-61-1259C>T		intron	N/A	ENSP00000377066.2
	IL1R2	ENST00000457817.5	TSL:2	c.-61-1259C>T		intron	N/A	ENSP00000408415.1

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17300 AN: 151996 Hom.: 1203 Cov.: 32

Gnomad AFR AF: 0.0912

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.0908

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0965

Gnomad OTH AF: 0.107

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

GnomAD4 genome AF: 0.114 AC: 17319 AN: 152114 Hom.: 1206 Cov.: 32 AF XY: 0.120 AC XY: 8917 AN XY: 74370

African (AFR) AF: 0.0913 AC: 3788 AN: 41508

American (AMR) AF: 0.120 AC: 1842 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0908 AC: 315 AN: 3468

East Asian (EAS) AF: 0.325 AC: 1670 AN: 5144

South Asian (SAS) AF: 0.206 AC: 991 AN: 4820

European-Finnish (FIN) AF: 0.170 AC: 1801 AN: 10580

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0965 AC: 6561 AN: 67984

Other (OTH) AF: 0.110 AC: 233 AN: 2114

Alfa AF: 0.104 Hom.: 146

Bravo AF: 0.110

Asia WGS AF: 0.281 AC: 975 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.47
DANN	Benign	0.60
PhyloP100		-1.1
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: rs719250; hg19: chr2-102623718;