2-102005914-A-G

Variant names:

• chr2-102005914-A-G
• rs4851527
• NM_004633.4:c.-61-2601A>G

Variant summary

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

The ENST00000332549.8(IL1R2):​c.-61-2601A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 152,150 control chromosomes in the GnomAD database, including 31,973 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 0.63 (31973 hom., cov: 32)
• Consequence: IL1R2 ENST00000332549.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.695
• Publications: 33 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 = 0.812 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000332549.8. 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.-61-2601A>G		intron	N/A	NP_004624.1
	IL1R2	NM_001261419.2		c.-61-2601A>G		intron	N/A	NP_001248348.1
	IL1R2	NR_048564.2		n.157-2601A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1R2	ENST00000332549.8	TSL:1 MANE Select	c.-61-2601A>G		intron	N/A	ENSP00000330959.3
	IL1R2	ENST00000393414.6	TSL:1	c.-61-2601A>G		intron	N/A	ENSP00000377066.2
	IL1R2	ENST00000457817.5	TSL:2	c.-61-2601A>G		intron	N/A	ENSP00000408415.1

Frequencies

GnomAD3 genomes AF: 0.633 AC: 96285 AN: 152032 Hom.: 31915 Cov.: 32

Gnomad AFR AF: 0.819

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.616

Gnomad ASJ AF: 0.492

Gnomad EAS AF: 0.775

Gnomad SAS AF: 0.646

Gnomad FIN AF: 0.723

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.592

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

GnomAD4 genome AF: 0.634 AC: 96404 AN: 152150 Hom.: 31973 Cov.: 32 AF XY: 0.644 AC XY: 47910 AN XY: 74368

African (AFR) AF: 0.820 AC: 34024 AN: 41518

American (AMR) AF: 0.616 AC: 9413 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.492 AC: 1706 AN: 3470

East Asian (EAS) AF: 0.775 AC: 4010 AN: 5176

South Asian (SAS) AF: 0.645 AC: 3113 AN: 4826

European-Finnish (FIN) AF: 0.723 AC: 7650 AN: 10580

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.510 AC: 34659 AN: 67982

Other (OTH) AF: 0.597 AC: 1261 AN: 2112

Alfa AF: 0.540 Hom.: 96027

Bravo AF: 0.636

Asia WGS AF: 0.755 AC: 2625 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.85
DANN	Benign	0.35
PhyloP100		-0.69
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: rs4851527; hg19: chr2-102622376; COSMIC: COSV60206369; COSMIC: COSV60206369;