chr2-112829856-C-G

Position:

• chr2-112829856-C-G

Variant summary

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

The NM_000576.3(IL1B):​c.*505G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 155,964 control chromosomes in the GnomAD database, including 3,233 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 (3151 hom., cov: 32)
  • Exomes 𝑓: 0.18 (82 hom.)
• Consequence: IL1B NM_000576.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.493

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=-0.83).
• 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.*505G>C		3_prime_UTR_variant	7/7	ENST00000263341.7
IL1B	XM_047444175.1	c.*505G>C		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1B	ENST00000263341.7	c.*505G>C		3_prime_UTR_variant	7/7	1	NM_000576.3	P1

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29823 AN: 151920 Hom.: 3146 Cov.: 32

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.0221

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.211

GnomAD4 exome AF: 0.182 AC: 715 AN: 3926 Hom.: 82 Cov.: 0 AF XY: 0.185 AC XY: 384 AN XY: 2076

Gnomad4 AFR exome AF: 0.0625

Gnomad4 AMR exome AF: 0.120

Gnomad4 ASJ exome AF: 0.286

Gnomad4 EAS exome AF: 0.00926

Gnomad4 SAS exome AF: 0.123

Gnomad4 FIN exome AF: 0.0833

Gnomad4 NFE exome AF: 0.227

Gnomad4 OTH exome AF: 0.205

GnomAD4 genome AF: 0.196 AC: 29840 AN: 152038 Hom.: 3151 Cov.: 32 AF XY: 0.195 AC XY: 14501 AN XY: 74330

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.174

Gnomad4 ASJ AF: 0.275

Gnomad4 EAS AF: 0.0224

Gnomad4 SAS AF: 0.153

Gnomad4 FIN AF: 0.249

Gnomad4 NFE AF: 0.235

Gnomad4 OTH AF: 0.211

Alfa AF: 0.220 Hom.: 552

Bravo AF: 0.187

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.41
DANN	Benign	0.44

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: rs1071676; hg19: chr2-113587433;