2-112830725-C-T

Position:

• chr2-112830725-C-T

Variant summary

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

The ENST00000263341.7(IL1B):​c.598-152G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 638,918 control chromosomes in the GnomAD database, including 36,859 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 0.29 (7191 hom., cov: 30)
  • Exomes 𝑓: 0.34 (29668 hom.)
• Consequence: IL1B ENST00000263341.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0300

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL1B	NM_000576.3	c.598-152G>A		intron_variant		ENST00000263341.7	NP_000567.1
IL1B	XM_047444175.1	c.364-152G>A		intron_variant			XP_047300131.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL1B	ENST00000263341.7	c.598-152G>A		intron_variant		1	NM_000576.3	ENSP00000263341	P1
IL1B	ENST00000491056.5	n.1405-152G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44511 AN: 151682 Hom.: 7195 Cov.: 30

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.519

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.315

GnomAD4 exome AF: 0.339 AC: 165091 AN: 487118 Hom.: 29668 AF XY: 0.334 AC XY: 86907 AN XY: 260396

Gnomad4 AFR exome AF: 0.166

Gnomad4 AMR exome AF: 0.291

Gnomad4 ASJ exome AF: 0.337

Gnomad4 EAS exome AF: 0.538

Gnomad4 SAS exome AF: 0.229

Gnomad4 FIN exome AF: 0.276

Gnomad4 NFE exome AF: 0.356

Gnomad4 OTH exome AF: 0.331

GnomAD4 genome AF: 0.293 AC: 44508 AN: 151800 Hom.: 7191 Cov.: 30 AF XY: 0.290 AC XY: 21498 AN XY: 74194

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.286

Gnomad4 ASJ AF: 0.333

Gnomad4 EAS AF: 0.520

Gnomad4 SAS AF: 0.237

Gnomad4 FIN AF: 0.269

Gnomad4 NFE AF: 0.359

Gnomad4 OTH AF: 0.311

Alfa AF: 0.296 Hom.: 965

Bravo AF: 0.293

Asia WGS AF: 0.322 AC: 1118 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.54
DANN	Benign	0.58

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: rs1143643; hg19: chr2-113588302; COSMIC: COSV54521285; COSMIC: COSV54521285;