2-102000742-T-C

Variant names:

• chr2-102000742-T-C
• rs7561460
• NM_004633.4:c.-61-7773T>C

Variant summary

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

The NM_004633.4(IL1R2):​c.-61-7773T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 150,900 control chromosomes in the GnomAD database, including 13,612 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 0.43 (13612 hom., cov: 31)
• Consequence: IL1R2 NM_004633.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.601
• Publications: 20 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.448 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1R2	NM_004633.4	MANE Select	c.-61-7773T>C		intron	N/A	NP_004624.1	P27930-1
	IL1R2	NM_001261419.2		c.-61-7773T>C		intron	N/A	NP_001248348.1	P27930-2
	IL1R2	NR_048564.2		n.156+1626T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1R2	ENST00000332549.8	TSL:1 MANE Select	c.-61-7773T>C		intron	N/A	ENSP00000330959.3	P27930-1
	IL1R2	ENST00000393414.6	TSL:1	c.-62+1626T>C		intron	N/A	ENSP00000377066.2	P27930-1
	IL1R2	ENST00000966319.1		c.-61-7773T>C		intron	N/A	ENSP00000636378.1

Frequencies

GnomAD3 genomes AF: 0.429 AC: 64733 AN: 150782 Hom.: 13597 Cov.: 31

Gnomad AFR AF: 0.453

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.458

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.556

Gnomad MID AF: 0.327

Gnomad NFE AF: 0.396

Gnomad OTH AF: 0.416

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

GnomAD4 genome AF: 0.429 AC: 64796 AN: 150900 Hom.: 13612 Cov.: 31 AF XY: 0.437 AC XY: 32275 AN XY: 73804

African (AFR) AF: 0.453 AC: 18642 AN: 41138

American (AMR) AF: 0.445 AC: 6754 AN: 15168

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 1159 AN: 3440

East Asian (EAS) AF: 0.458 AC: 2348 AN: 5130

South Asian (SAS) AF: 0.426 AC: 2038 AN: 4788

European-Finnish (FIN) AF: 0.556 AC: 5843 AN: 10510

Middle Eastern (MID) AF: 0.345 AC: 100 AN: 290

European-Non Finnish (NFE) AF: 0.396 AC: 26707 AN: 67448

Other (OTH) AF: 0.419 AC: 874 AN: 2084

Alfa AF: 0.408 Hom.: 40145

Bravo AF: 0.431

Asia WGS AF: 0.452 AC: 1573 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.1
DANN	Benign	0.60
PhyloP100		-0.60
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: rs7561460; hg19: chr2-102617204; COSMIC: COSV60206340; COSMIC: COSV60206340;