rs568715066

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000576.3(IL1B):​c.160G>C​(p.Asp54His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

IL1B
NM_000576.3 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.130
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.033827186).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IL1BNM_000576.3 linkc.160G>C p.Asp54His missense_variant Exon 4 of 7 ENST00000263341.7 NP_000567.1 P01584

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IL1BENST00000263341.7 linkc.160G>C p.Asp54His missense_variant Exon 4 of 7 1 NM_000576.3 ENSP00000263341.2 P01584

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.072
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.55
CADD
Benign
4.0
DANN
Benign
0.65
DEOGEN2
Benign
0.11
T;T;.;T
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.0045
N
LIST_S2
Benign
0.21
T;T;T;T
M_CAP
Benign
0.0026
T
MetaRNN
Benign
0.034
T;T;T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
-1.6
N;.;.;.
PrimateAI
Benign
0.24
T
PROVEAN
Benign
4.2
N;N;N;N
REVEL
Benign
0.078
Sift
Benign
1.0
T;T;T;T
Sift4G
Benign
1.0
T;T;.;T
Polyphen
0.0
B;.;.;.
Vest4
0.094
MutPred
0.52
Loss of ubiquitination at K59 (P = 0.037);Loss of ubiquitination at K59 (P = 0.037);Loss of ubiquitination at K59 (P = 0.037);Loss of ubiquitination at K59 (P = 0.037);
MVP
0.38
MPC
0.47
ClinPred
0.042
T
GERP RS
1.7
Varity_R
0.032
gMVP
0.24

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: rs568715066; hg19: chr2-113591092; API