chr2-112832813-G-A

Variant names:

• chr2-112832813-G-A
• rs1143634
• NM_000576.3:c.315C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_000576.3(IL1B):​c.315C>T​(p.Phe105Phe) 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
• Clinical Significance: Benign; Affects; association; other no assertion criteria provided B:1 O:3
• Conservation: PhyloP100: -0.677
• Publications: 1252 publications found

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 Gene-Disease associations (from GenCC):

• hereditary diffuse gastric adenocarcinoma

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000299339 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 869137.Status of the report is no_assertion_criteria_provided, 0 stars.
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000576.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1B	NM_000576.3	MANE Select	c.315C>T	p.Phe105Phe	synonymous	Exon 5 of 7	NP_000567.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1B	ENST00000263341.7	TSL:1 MANE Select	c.315C>T	p.Phe105Phe	synonymous	Exon 5 of 7	ENSP00000263341.2
	IL1B	ENST00000491056.5	TSL:1	n.1122C>T		non_coding_transcript_exon	Exon 4 of 6
	IL1B	ENST00000418817.5	TSL:3	c.315C>T	p.Phe105Phe	synonymous	Exon 5 of 5	ENSP00000407219.1

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

GnomAD2 exomes AF: 0.192 AC: 48238 AN: 251472 AF XY: 0.197

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 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

African (AFR) AF: 0.135 AC: 4505 AN: 33466

American (AMR) AF: 0.117 AC: 5237 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 7272 AN: 26130

East Asian (EAS) AF: 0.0332 AC: 1318 AN: 39700

South Asian (SAS) AF: 0.166 AC: 14325 AN: 86246

European-Finnish (FIN) AF: 0.251 AC: 13391 AN: 53418

Middle Eastern (MID) AF: 0.314 AC: 1812 AN: 5768

European-Non Finnish (NFE) AF: 0.236 AC: 262323 AN: 1111356

Other (OTH) AF: 0.213 AC: 12834 AN: 60370

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

African (AFR) AF: 0.132 AC: 5483 AN: 41514

American (AMR) AF: 0.172 AC: 2626 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 948 AN: 3468

East Asian (EAS) AF: 0.0222 AC: 115 AN: 5188

South Asian (SAS) AF: 0.150 AC: 725 AN: 4818

European-Finnish (FIN) AF: 0.248 AC: 2623 AN: 10562

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.234 AC: 15927 AN: 67982

Other (OTH) AF: 0.207 AC: 437 AN: 2112

Alfa AF: 0.220 Hom.: 14334

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:1 Other:3

Revision: no assertion criteria provided

Submissions by phenotype

IL1B-related disorder Benign:1

Nov 19, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

Feb 10, 2020

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

Significance: association

Review Status: no assertion criteria provided

Collection Method: case-control

Endometriosis Other:1

Oct 20, 2021

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

Significance: Affects

Review Status: no assertion criteria provided

Collection Method: case-control

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

Dec 10, 2022

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

Significance: other

Review Status: no assertion criteria provided

Collection Method: research

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.1
DANN	Benign	0.82
PhyloP100		-0.68
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1143634; hg19: chr2-113590390; COSMIC: COSV54523425; COSMIC: COSV54523425;