rs3136558

chr2-112833698-A-G

Variant summary

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

The NM_000576.3(IL1B):c.100-123T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 937,372 control chromosomes in the GnomAD database, including 27,933 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 0.22 (3836 hom., cov: 32)
  • Exomes 𝑓: 0.24 (24097 hom.)
• Consequence: IL1B NM_000576.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0500

Genes affected

IL1B (HGNC:5992): (interleukin 1 beta) The protein encoded by this gene is a member of the interleukin 1 cytokine family. This cytokine is produced by activated macrophages as a proprotein, which is proteolytically processed to its active form by caspase 1 (CASP1/ICE). This cytokine is an important mediator of the inflammatory response, and is involved in a variety of cellular activities, including cell proliferation, differentiation, and apoptosis. The induction of cyclooxygenase-2 (PTGS2/COX2) by this cytokine in the central nervous system (CNS) is found to contribute to inflammatory pain hypersensitivity. Similarly, IL-1B has been implicated in human osteoarthritis pathogenesis. Patients with severe Coronavirus Disease 2019 (COVID-19) present elevated levels of pro-inflammatory cytokines such as IL-1B in bronchial alveolar lavage fluid samples. The lung damage induced by the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is to a large extent, a result of the inflammatory response promoted by cytokines such as IL-1B. This gene and eight other interleukin 1 family genes form a cytokine gene cluster on chromosome 2. [provided by RefSeq, Jul 2020]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1B	NM_000576.3	c.100-123T>C		intron_variant		ENST00000263341.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1B	ENST00000263341.7	c.100-123T>C		intron_variant		1	NM_000576.3	P1

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33066 AN: 151950 Hom.: 3829 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.317

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.233

GnomAD4 exome AF: 0.238 AC: 186598 AN: 785302 Hom.: 24097 AF XY: 0.235 AC XY: 96308 AN XY: 410408

Gnomad4 AFR exome AF: 0.146

Gnomad4 AMR exome AF: 0.344

Gnomad4 ASJ exome AF: 0.248

Gnomad4 EAS exome AF: 0.453

Gnomad4 SAS exome AF: 0.188

Gnomad4 FIN exome AF: 0.273

Gnomad4 NFE exome AF: 0.224

Gnomad4 OTH exome AF: 0.236

GnomAD4 genome AF: 0.217 AC: 33072 AN: 152070 Hom.: 3836 Cov.: 32 AF XY: 0.219 AC XY: 16284 AN XY: 74332

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.270

Gnomad4 ASJ AF: 0.245

Gnomad4 EAS AF: 0.395

Gnomad4 SAS AF: 0.176

Gnomad4 FIN AF: 0.265

Gnomad4 NFE AF: 0.224

Gnomad4 OTH AF: 0.230

Alfa AF: 0.226 Hom.: 4608

Bravo AF: 0.221

Asia WGS AF: 0.285 AC: 991 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	2.6
Dann	Benign	0.51

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: rs3136558; hg19: chr2-113591275;