rs144433180

Variant names:

• chr2-112831327-C-A
• rs144433180
• NM_000576.3:c.562G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-112831327-C-A
• chr2-112831327-C-G
• chr2-112831327-C-T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_000576.3(IL1B):​c.562G>T​(p.Val188Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,461,770 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V188M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: IL1B NM_000576.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.725
• Publications: 6 publications found

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)

ENSG00000299339 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2773674).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000576.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1B	NM_000576.3	MANE Select	c.562G>T	p.Val188Leu	missense	Exon 6 of 7	NP_000567.1	P01584

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1B	ENST00000263341.7	TSL:1 MANE Select	c.562G>T	p.Val188Leu	missense	Exon 6 of 7	ENSP00000263341.2	P01584
	IL1B	ENST00000491056.5	TSL:1	n.1369G>T		non_coding_transcript_exon	Exon 5 of 6
	IL1B	ENST00000487639.1	TSL:3	n.463G>T		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000358 AC: 9 AN: 251494 AF XY: 0.0000441

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000489

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000103 AC: 15 AN: 1461770 Hom.: 0 Cov.: 32 AF XY: 0.0000110 AC XY: 8 AN XY: 727186

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.000252 AC: 10 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111922

Other (OTH) AF: 0.0000662 AC: 4 AN: 60384

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000340

ExAC AF: 0.0000247 AC: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.37	T
Eigen	Benign	-0.054
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.20	N
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Pathogenic	3.4	M
PhyloP100		0.72
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.13
Sift	Benign	0.055	T
Sift4G	Benign	0.44	T
Polyphen		0.97	D
Vest4		0.28
MutPred		0.68		Gain of catalytic residue at V188 (P = 0.0305)
MVP		0.58
MPC		0.51
ClinPred		0.40	T
GERP RS		2.7
Varity_R		0.41
gMVP		0.56
Mutation Taster		=87/13	polymorphism

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

Other links and lift over

dbSNP: rs144433180; hg19: chr2-113588904;