chr2-112832813-G-A

Position:

chr2-112832813-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

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,Affects,association,other (no stars).

Frequency

Genomes: 𝑓 0.19 ( 3058 hom., cov: 32)

Exomes 𝑓: 0.22 ( 37679 hom. )

Consequence

IL1B
NM_000576.3 synonymous

Scores

Clinical Significance

Benign; Affects; association; other no assertion criteria provided B:1O:3

Conservation

PhyloP100: -0.677

Variant links:

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]

IL1B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 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, Affects, association, other]. Clinvar id is 869137.Status of the report is no_assertion_criteria_provided, 0 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 linkuse as main transcript	c.315C>T	p.Phe105=	synonymous_variant	5/7	ENST00000263341.7
IL1B	XM_047444175.1 linkuse as main transcript	c.81C>T	p.Phe27=	synonymous_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1B	ENST00000263341.7 linkuse as main transcript	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.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.221

AC XY:

160625

AN XY:

726932

show subpopulations

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.:

AF XY:

0.191

AC XY:

14216

AN XY:

74384

show subpopulations

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; Affects; association; other

Submissions summary: Benign:1Other:3

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

IL1B-related disorder

Benign:1

Benign, no assertion criteria provided

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over