2-112832813-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_000576.3(IL1B):c.315C>T(p.Phe105=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 1,613,312 control chromosomes in the GnomAD database, including 40,737 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.19 (3058 hom., cov: 32)
  • Exomes 𝑓: 0.22 (37679 hom.)
• Consequence: IL1B NM_000576.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1 O:3
• Conservation: PhyloP100: -0.677

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 2-112832813-G-A is Benign according to our data. Variant chr2-112832813-G-A is described in ClinVar as [Benign]. Clinvar id is 869137.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-112832813-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.677 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1B	NM_000576.3	c.315C>T	p.Phe105=	synonymous_variant	5/7	ENST00000263341.7
IL1B	XM_047444175.1	c.81C>T	p.Phe27=	synonymous_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1B	ENST00000263341.7	c.315C>T	p.Phe105=	synonymous_variant	5/7	1	NM_000576.3	P1

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29258 AN: 152020 Hom.: 3053 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.0219

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.208

GnomAD3 exomes AF: 0.192 AC: 48238 AN: 251472 Hom.: 5342 AF XY: 0.197 AC XY: 26721 AN XY: 135910

Gnomad AFR exome AF: 0.131

Gnomad AMR exome AF: 0.113

Gnomad ASJ exome AF: 0.281

Gnomad EAS exome AF: 0.0195

Gnomad SAS exome AF: 0.164

Gnomad FIN exome AF: 0.244

Gnomad NFE exome AF: 0.241

Gnomad OTH exome AF: 0.219

GnomAD4 exome AF: 0.221 AC: 323017 AN: 1461174 Hom.: 37679 Cov.: 34 AF XY: 0.221 AC XY: 160625 AN XY: 726932

Gnomad4 AFR exome AF: 0.135

Gnomad4 AMR exome AF: 0.117

Gnomad4 ASJ exome AF: 0.278

Gnomad4 EAS exome AF: 0.0332

Gnomad4 SAS exome AF: 0.166

Gnomad4 FIN exome AF: 0.251

Gnomad4 NFE exome AF: 0.236

Gnomad4 OTH exome AF: 0.213

GnomAD4 genome AF: 0.192 AC: 29277 AN: 152138 Hom.: 3058 Cov.: 32 AF XY: 0.191 AC XY: 14216 AN XY: 74384

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.172

Gnomad4 ASJ AF: 0.273

Gnomad4 EAS AF: 0.0222

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.248

Gnomad4 NFE AF: 0.234

Gnomad4 OTH AF: 0.207

Alfa AF: 0.226 Hom.: 7194

Bravo AF: 0.182

Asia WGS AF: 0.114 AC: 397 AN: 3478

EpiCase AF: 0.239

EpiControl AF: 0.239

ClinVar

Significance: Benign

Submissions summary: Benign:1 Other:3

Revision: criteria provided, single submitter

Submissions by phenotype

IL1B-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 19, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Antisynthetase syndrome Other:1

association, no assertion criteria provided

case-control

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

Feb 10, 2020

- -

Endometriosis Other:1

Affects, no assertion criteria provided

case-control

Laboratorio de Investigación del Departamento de Salud, Universidad Iberoamericana A.C.

Oct 20, 2021

Mexican mestizo women with severe stage of endometriosis have higher frequencies of TNF*2-, IL1B*2- and IL1RN*2-alleles, which may explain a possible correlation with disease severity rather than predisposition or risk. -

Cholangiocarcinoma Other:1

other, no assertion criteria provided

research

Department of Surgery, Campus Charité Mitte Campus Virchow-klinikum, Charite-Universitaetsmedizin Berlin

Dec 10, 2022

C/C genotype associated with significantly shorter OS after surgical resection of intrahepatic CCA C/C genotype associated with shorter overall survival

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	2.1
Dann	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1143634; hg19: chr2-113590390; COSMIC: COSV54523425; COSMIC: COSV54523425;