2-112830725-C-T

Variant names:

• chr2-112830725-C-T
• rs1143643
• NM_000576.3:c.598-152G>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.598-152G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 638,918 control chromosomes in the GnomAD database, including 36,859 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 0.29 (7191 hom., cov: 30)
  • Exomes 𝑓: 0.34 (29668 hom.)
• Consequence: IL1B NM_000576.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0300
• Publications: 110 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.503 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.598-152G>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.598-152G>A		intron	N/A	ENSP00000263341.2	P01584
	IL1B	ENST00000491056.5	TSL:1	n.1405-152G>A		intron	N/A
	ENSG00000299339	ENST00000762706.1		n.405-54533C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44511 AN: 151682 Hom.: 7195 Cov.: 30

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.519

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.315

GnomAD4 exome AF: 0.339 AC: 165091 AN: 487118 Hom.: 29668 AF XY: 0.334 AC XY: 86907 AN XY: 260396

African (AFR) AF: 0.166 AC: 2212 AN: 13352

American (AMR) AF: 0.291 AC: 6552 AN: 22516

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 5084 AN: 15072

East Asian (EAS) AF: 0.538 AC: 17071 AN: 31750

South Asian (SAS) AF: 0.229 AC: 11283 AN: 49280

European-Finnish (FIN) AF: 0.276 AC: 8938 AN: 32356

Middle Eastern (MID) AF: 0.265 AC: 930 AN: 3510

European-Non Finnish (NFE) AF: 0.356 AC: 103843 AN: 291564

Other (OTH) AF: 0.331 AC: 9178 AN: 27718

GnomAD4 genome AF: 0.293 AC: 44508 AN: 151800 Hom.: 7191 Cov.: 30 AF XY: 0.290 AC XY: 21498 AN XY: 74194

African (AFR) AF: 0.167 AC: 6908 AN: 41388

American (AMR) AF: 0.286 AC: 4355 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 1156 AN: 3470

East Asian (EAS) AF: 0.520 AC: 2669 AN: 5134

South Asian (SAS) AF: 0.237 AC: 1142 AN: 4822

European-Finnish (FIN) AF: 0.269 AC: 2822 AN: 10490

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.359 AC: 24390 AN: 67934

Other (OTH) AF: 0.311 AC: 657 AN: 2112

Alfa AF: 0.320 Hom.: 2576

Bravo AF: 0.293

Asia WGS AF: 0.322 AC: 1118 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.54
DANN	Benign	0.58
PhyloP100		-0.030
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: rs1143643; hg19: chr2-113588302; COSMIC: COSV54521285; COSMIC: COSV54521285;