rs1143639

chr2-112831216-C-T

Variant summary

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

The NM_000576.3(IL1B):c.597+76G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 1,546,724 control chromosomes in the GnomAD database, including 39,101 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 0.20 (3135 hom., cov: 31)
  • Exomes 𝑓: 0.22 (35966 hom.)
• Consequence: IL1B NM_000576.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.899

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1B	NM_000576.3	c.597+76G>A		intron_variant		ENST00000263341.7
IL1B	XM_047444175.1	c.363+76G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1B	ENST00000263341.7	c.597+76G>A		intron_variant		1	NM_000576.3	P1
IL1B	ENST00000491056.5	n.1404+76G>A		intron_variant, non_coding_transcript_variant		1
IL1B	ENST00000487639.1	n.574G>A		non_coding_transcript_exon_variant	3/3	3

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29729 AN: 151820 Hom.: 3130 Cov.: 31

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.318

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.0217

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.210

GnomAD4 exome AF: 0.221 AC: 307607 AN: 1394784 Hom.: 35966 Cov.: 21 AF XY: 0.221 AC XY: 153786 AN XY: 697348

Gnomad4 AFR exome AF: 0.142

Gnomad4 AMR exome AF: 0.118

Gnomad4 ASJ exome AF: 0.278

Gnomad4 EAS exome AF: 0.0333

Gnomad4 SAS exome AF: 0.168

Gnomad4 FIN exome AF: 0.251

Gnomad4 NFE exome AF: 0.235

Gnomad4 OTH exome AF: 0.214

GnomAD4 genome AF: 0.196 AC: 29747 AN: 151940 Hom.: 3135 Cov.: 31 AF XY: 0.195 AC XY: 14456 AN XY: 74266

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.172

Gnomad4 ASJ AF: 0.274

Gnomad4 EAS AF: 0.0220

Gnomad4 SAS AF: 0.153

Gnomad4 FIN AF: 0.248

Gnomad4 NFE AF: 0.235

Gnomad4 OTH AF: 0.209

Alfa AF: 0.233 Hom.: 1514

Bravo AF: 0.186

Asia WGS AF: 0.115 AC: 400 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.21
Dann	Benign	0.59

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: rs1143639; hg19: chr2-113588793; COSMIC: COSV54521174; COSMIC: COSV54521174;