rs138009692

Variant summary

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

The NM_000576.3(IL1B):​c.630G>T​(p.Lys210Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000131 in 1,526,938 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 𝑓 0.0000087 ( 0 hom., cov: 30)
Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

IL1B
NM_000576.3 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.517
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 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=0.051297396).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IL1BNM_000576.3 linkc.630G>T p.Lys210Asn missense_variant Exon 7 of 7 ENST00000263341.7 NP_000567.1 P01584
IL1BXM_047444175.1 linkc.396G>T p.Lys132Asn missense_variant Exon 4 of 4 XP_047300131.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IL1BENST00000263341.7 linkc.630G>T p.Lys210Asn missense_variant Exon 7 of 7 1 NM_000576.3 ENSP00000263341.2 P01584
IL1BENST00000491056.5 linkn.1437G>T non_coding_transcript_exon_variant Exon 6 of 6 1

Frequencies

GnomAD3 genomes
AF:
0.00000866
AC:
1
AN:
115422
Hom.:
0
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000271
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
7.08e-7
AC:
1
AN:
1411516
Hom.:
0
Cov.:
31
AF XY:
0.00000143
AC XY:
1
AN XY:
701484
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000127
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000866
AC:
1
AN:
115422
Hom.:
0
Cov.:
30
AF XY:
0.0000175
AC XY:
1
AN XY:
57042
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000271
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.42
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.72
CADD
Benign
16
DANN
Benign
0.96
DEOGEN2
Benign
0.12
T
Eigen
Benign
-0.71
Eigen_PC
Benign
-0.62
FATHMM_MKL
Benign
0.12
N
LIST_S2
Benign
0.74
T
M_CAP
Benign
0.0034
T
MetaRNN
Benign
0.051
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.4
L
PrimateAI
Benign
0.40
T
PROVEAN
Benign
-0.15
N
REVEL
Benign
0.097
Sift
Benign
0.46
T
Sift4G
Benign
0.49
T
Polyphen
0.0040
B
Vest4
0.10
MutPred
0.40
Loss of MoRF binding (P = 0.051);
MVP
0.49
MPC
0.48
ClinPred
0.11
T
GERP RS
-1.7
Varity_R
0.30
gMVP
0.66

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: rs138009692; hg19: chr2-113588118; API