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rs1143634

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

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

Scores

2

Clinical Significance

Benign criteria provided, single submitter 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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
IL1BNM_000576.3 linkuse as main transcriptc.315C>T p.Phe105= synonymous_variant 5/7 ENST00000263341.7
IL1BXM_047444175.1 linkuse as main transcriptc.81C>T p.Phe27= synonymous_variant 2/4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IL1BENST00000263341.7 linkuse as main transcriptc.315C>T p.Phe105= synonymous_variant 5/71 NM_000576.3 P1

Frequencies

GnomAD3 genomes
AF:
0.192
AC:
29258
AN:
152020
Hom.:
3053
Cov.:
32
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.:
34
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.:
32
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
Submissions summary: Benign:1Other:3
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

IL1B-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesNov 19, 2019This 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 providedcase-controlHLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio VillegasFeb 10, 2020- -
Endometriosis Other:1
Affects, no assertion criteria providedcase-controlLaboratorio de Investigación del Departamento de Salud, Universidad Iberoamericana A.C.Oct 20, 2021Mexican 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 providedresearchDepartment of Surgery, Campus Charité Mitte Campus Virchow-klinikum, Charite-Universitaetsmedizin BerlinDec 10, 2022C/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.

Other links and lift over

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