rs3917354

chr2-112835315-GA-Gchr2-112835315-GA-GAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000576.3(IL1B):c.99+250del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 559,934 control chromosomes in the GnomAD database, including 9,795 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.16 (2226 hom., cov: 29)
  • Exomes 𝑓: 0.18 (7569 hom.)
• Consequence: IL1B NM_000576.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00400

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1B	NM_000576.3	c.99+250del		intron_variant		ENST00000263341.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1B	ENST00000263341.7	c.99+250del		intron_variant		1	NM_000576.3	P1

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24256 AN: 152038 Hom.: 2225 Cov.: 29

Gnomad AFR AF: 0.0810

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.0437

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.173

GnomAD4 exome AF: 0.183 AC: 74739 AN: 407778 Hom.: 7569 Cov.: 0 AF XY: 0.182 AC XY: 39329 AN XY: 215792

Gnomad4 AFR exome AF: 0.0820

Gnomad4 AMR exome AF: 0.114

Gnomad4 ASJ exome AF: 0.246

Gnomad4 EAS exome AF: 0.0469

Gnomad4 SAS exome AF: 0.141

Gnomad4 FIN exome AF: 0.214

Gnomad4 NFE exome AF: 0.209

Gnomad4 OTH exome AF: 0.188

GnomAD4 genome AF: 0.159 AC: 24255 AN: 152156 Hom.: 2226 Cov.: 29 AF XY: 0.157 AC XY: 11645 AN XY: 74374

Gnomad4 AFR AF: 0.0809

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.252

Gnomad4 EAS AF: 0.0436

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.206

Gnomad4 NFE AF: 0.208

Gnomad4 OTH AF: 0.173

Alfa AF: 0.184 Hom.: 344

Bravo AF: 0.150

Asia WGS AF: 0.107 AC: 369 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs3917354; hg19: chr2-113592892;