rs4851526

chr2-102001908-A-G

Variant summary

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

The NM_004633.4(IL1R2):c.-61-6607A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 151,948 control chromosomes in the GnomAD database, including 15,772 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 0.45 (15772 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: IL1R2 NM_004633.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.323

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1R2	NM_004633.4	c.-61-6607A>G		intron_variant		ENST00000332549.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1R2	ENST00000332549.8	c.-61-6607A>G		intron_variant		1	NM_004633.4	P1
IL1R2	ENST00000393414.6	c.-62+2792A>G		intron_variant		1		P1
IL1R2	ENST00000464994.5	n.75-6607A>G		intron_variant, non_coding_transcript_variant		3
IL1R2	ENST00000493749.1	n.53-6607A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68509 AN: 151832 Hom.: 15755 Cov.: 32

Gnomad AFR AF: 0.518

Gnomad AMI AF: 0.372

Gnomad AMR AF: 0.456

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.453

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.551

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.403

Gnomad OTH AF: 0.432

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

GnomAD4 genome AF: 0.451 AC: 68568 AN: 151948 Hom.: 15772 Cov.: 32 AF XY: 0.458 AC XY: 33998 AN XY: 74264

Gnomad4 AFR AF: 0.517

Gnomad4 AMR AF: 0.456

Gnomad4 ASJ AF: 0.342

Gnomad4 EAS AF: 0.453

Gnomad4 SAS AF: 0.430

Gnomad4 FIN AF: 0.551

Gnomad4 NFE AF: 0.403

Gnomad4 OTH AF: 0.435

Alfa AF: 0.419 Hom.: 6958

Bravo AF: 0.449

Asia WGS AF: 0.458 AC: 1596 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	7.0
Dann	Benign	0.65

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: rs4851526; hg19: chr2-102618370; COSMIC: COSV60206355; COSMIC: COSV60206355;