2-112832813-G-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000576.3(IL1B):​c.315C>G​(p.Phe105Leu) 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. 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. Synonymous variant affecting the same amino acid position (i.e. F105F) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IL1B NM_000576.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.677

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13054168).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1B	NM_000576.3	c.315C>G	p.Phe105Leu	missense_variant	Exon 5 of 7	ENST00000263341.7	NP_000567.1
IL1B	XM_047444175.1	c.81C>G	p.Phe27Leu	missense_variant	Exon 2 of 4		XP_047300131.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1B	ENST00000263341.7	c.315C>G	p.Phe105Leu	missense_variant	Exon 5 of 7	1	NM_000576.3	ENSP00000263341.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.13
DANN	Benign	0.59
DEOGEN2	Benign	0.22	T;T;.;T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.050	N
LIST_S2	Benign	0.46	T;T;T;T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.13	T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.34	N;.;.;.
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.39	N;N;N;N
REVEL	Benign	0.050
Sift	Benign	0.57	T;T;T;T
Sift4G	Benign	0.71	T;T;.;T
Polyphen		0.0	B;.;.;.
Vest4		0.088
MutPred		0.65		Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);
MVP		0.39
MPC		0.46
ClinPred		0.023	T
GERP RS		-4.7
Varity_R		0.033
gMVP		0.31

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-113590390;