chr2-102018599-C-T

Position:

• chr2-102018599-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004633.4(IL1R2):​c.514-1039C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 152,158 control chromosomes in the GnomAD database, including 4,722 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 0.23 (4722 hom., cov: 33)
• Consequence: IL1R2 NM_004633.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.488

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL1R2	NM_004633.4	c.514-1039C>T		intron_variant		ENST00000332549.8	NP_004624.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL1R2	ENST00000332549.8	c.514-1039C>T		intron_variant		1	NM_004633.4	ENSP00000330959	P1
IL1R2	ENST00000393414.6	c.514-1039C>T		intron_variant		1		ENSP00000377066	P1
IL1R2	ENST00000441002.1	c.514-1039C>T		intron_variant		1		ENSP00000414611
IL1R2	ENST00000457817.5	c.514-1039C>T		intron_variant		2		ENSP00000408415

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34348 AN: 152038 Hom.: 4716 Cov.: 33

Gnomad AFR AF: 0.0889

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.251

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.210

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.237

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

GnomAD4 genome AF: 0.226 AC: 34361 AN: 152158 Hom.: 4722 Cov.: 33 AF XY: 0.233 AC XY: 17318 AN XY: 74370

Gnomad4 AFR AF: 0.0887

Gnomad4 AMR AF: 0.270

Gnomad4 ASJ AF: 0.211

Gnomad4 EAS AF: 0.252

Gnomad4 SAS AF: 0.126

Gnomad4 FIN AF: 0.450

Gnomad4 NFE AF: 0.270

Gnomad4 OTH AF: 0.235

Alfa AF: 0.184 Hom.: 515

Bravo AF: 0.211

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.48
DANN	Benign	0.68

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

Publications

LitVar

Other links and lift over

dbSNP: rs3218934; hg19: chr2-102635061; COSMIC: COSV60206413; COSMIC: COSV60206413;