2-112834078-T-G

Variant names:

• chr2-112834078-T-G
• rs1143630
• NM_000576.3:c.100-503A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000576.3(IL1B):​c.100-503A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.874 in 152,192 control chromosomes in the GnomAD database, including 58,708 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.87 (58708 hom., cov: 32)
• Consequence: IL1B NM_000576.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.434
• Publications: 45 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.932 is higher than 0.05.

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.100-503A>C		intron	N/A	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.100-503A>C		intron	N/A	ENSP00000263341.2	P01584
	IL1B	ENST00000491056.5	TSL:1	n.650-503A>C		intron	N/A
	IL1B	ENST00000418817.5	TSL:3	c.100-503A>C		intron	N/A	ENSP00000407219.1	C9JWV2

Frequencies

GnomAD3 genomes AF: 0.874 AC: 132969 AN: 152074 Hom.: 58667 Cov.: 32

Gnomad AFR AF: 0.743

Gnomad AMI AF: 0.993

Gnomad AMR AF: 0.917

Gnomad ASJ AF: 0.871

Gnomad EAS AF: 0.836

Gnomad SAS AF: 0.861

Gnomad FIN AF: 0.933

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.938

Gnomad OTH AF: 0.876

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.874 AC: 133063 AN: 152192 Hom.: 58708 Cov.: 32 AF XY: 0.875 AC XY: 65125 AN XY: 74424

African (AFR) AF: 0.743 AC: 30822 AN: 41470

American (AMR) AF: 0.918 AC: 14027 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.871 AC: 3020 AN: 3468

East Asian (EAS) AF: 0.836 AC: 4336 AN: 5186

South Asian (SAS) AF: 0.860 AC: 4153 AN: 4828

European-Finnish (FIN) AF: 0.933 AC: 9901 AN: 10614

Middle Eastern (MID) AF: 0.827 AC: 243 AN: 294

European-Non Finnish (NFE) AF: 0.938 AC: 63806 AN: 68018

Other (OTH) AF: 0.875 AC: 1849 AN: 2114

Alfa AF: 0.917 Hom.: 50143

Bravo AF: 0.868

Asia WGS AF: 0.828 AC: 2879 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.1
DANN	Benign	0.35
PhyloP100		0.43
Mutation Taster		=100/0	polymorphism (auto)

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: rs1143630; hg19: chr2-113591655;