rs1143634

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

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

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.677

Publications

1252 publications found

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 Gene-Disease associations (from GenCC):

hereditary diffuse gastric adenocarcinoma
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

IL1B links:

ENSG00000299339 (HGNC:):

ENSG00000299339 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1B	NM_000576.3 link	c.315C>T	p.Phe105Phe	synonymous_variant	Exon 5 of 7	ENST00000263341.7	NP_000567.1
IL1B	XM_047444175.1 link	c.81C>T	p.Phe27Phe	synonymous_variant	Exon 2 of 4		XP_047300131.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1B	ENST00000263341.7 link	c.315C>T	p.Phe105Phe	synonymous_variant	Exon 5 of 7	1	NM_000576.3	ENSP00000263341.2

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

GnomAD2 exomes

AF:

0.192

AC:

48238

AN:

251472

AF XY:

0.197

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 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

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

12932

25865

38797

51730

64662

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8736

17472

26208

34944

43680

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.192

AC:

29277

AN:

152138

Hom.:

3058

Cov.:

AF XY:

0.191

AC XY:

14216

AN XY:

74384

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1192

2384

3577

4769

5961

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

312

624

936

1248

1560

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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:1Other:3

Revision: no assertion criteria provided

LINK: link

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.1

(source)

DANN

Benign

0.82

PhyloP100

-0.68

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over