2-112832890-C-T

Variant names:

• chr2-112832890-C-T
• rs1143633
• NM_000576.3:c.302-64G>A

Variant summary

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

The NM_000576.3(IL1B):​c.302-64G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 1,568,952 control chromosomes in the GnomAD database, including 95,129 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 0.31 (7669 hom., cov: 32)
  • Exomes 𝑓: 0.35 (87460 hom.)
• Consequence: IL1B NM_000576.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.479
• Publications: 133 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.547 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.302-64G>A		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.302-64G>A		intron	N/A	ENSP00000263341.2	P01584
	IL1B	ENST00000491056.5	TSL:1	n.1109-64G>A		intron	N/A
	IL1B	ENST00000418817.5	TSL:3	c.302-64G>A		intron	N/A	ENSP00000407219.1	C9JWV2

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46546 AN: 151916 Hom.: 7670 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.332

Gnomad EAS AF: 0.564

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.264

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.318

GnomAD4 exome AF: 0.347 AC: 491220 AN: 1416918 Hom.: 87460 Cov.: 24 AF XY: 0.344 AC XY: 243579 AN XY: 707454

African (AFR) AF: 0.200 AC: 6522 AN: 32642

American (AMR) AF: 0.295 AC: 13082 AN: 44394

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 8702 AN: 25818

East Asian (EAS) AF: 0.574 AC: 22671 AN: 39488

South Asian (SAS) AF: 0.245 AC: 20886 AN: 85164

European-Finnish (FIN) AF: 0.280 AC: 14777 AN: 52852

Middle Eastern (MID) AF: 0.261 AC: 1450 AN: 5560

European-Non Finnish (NFE) AF: 0.357 AC: 382914 AN: 1072112

Other (OTH) AF: 0.343 AC: 20216 AN: 58888

GnomAD4 genome AF: 0.306 AC: 46563 AN: 152034 Hom.: 7669 Cov.: 32 AF XY: 0.303 AC XY: 22515 AN XY: 74314

African (AFR) AF: 0.209 AC: 8661 AN: 41486

American (AMR) AF: 0.288 AC: 4400 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.332 AC: 1152 AN: 3470

East Asian (EAS) AF: 0.565 AC: 2914 AN: 5162

South Asian (SAS) AF: 0.254 AC: 1226 AN: 4820

European-Finnish (FIN) AF: 0.268 AC: 2832 AN: 10560

Middle Eastern (MID) AF: 0.267 AC: 78 AN: 292

European-Non Finnish (NFE) AF: 0.358 AC: 24346 AN: 67950

Other (OTH) AF: 0.313 AC: 660 AN: 2106

Alfa AF: 0.343 Hom.: 35978

Bravo AF: 0.308

Asia WGS AF: 0.339 AC: 1180 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.5
DANN	Benign	0.55
PhyloP100		-0.48
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: rs1143633; hg19: chr2-113590467; COSMIC: COSV54521294; COSMIC: COSV54521294;