2-112833698-A-G

Variant names:

• chr2-112833698-A-G
• rs3136558
• NM_000576.3:c.100-123T>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.100-123T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 937,372 control chromosomes in the GnomAD database, including 27,933 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 0.22 (3836 hom., cov: 32)
  • Exomes 𝑓: 0.24 (24097 hom.)
• Consequence: IL1B NM_000576.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0500
• Publications: 58 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.381 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1B	NM_000576.3	MANE Select	c.100-123T>C		intron	N/A	NP_000567.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1B	ENST00000263341.7	TSL:1 MANE Select	c.100-123T>C		intron	N/A	ENSP00000263341.2
	IL1B	ENST00000491056.5	TSL:1	n.650-123T>C		intron	N/A
	IL1B	ENST00000418817.5	TSL:3	c.100-123T>C		intron	N/A	ENSP00000407219.1

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33066 AN: 151950 Hom.: 3829 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.317

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.233

GnomAD4 exome AF: 0.238 AC: 186598 AN: 785302 Hom.: 24097 AF XY: 0.235 AC XY: 96308 AN XY: 410408

African (AFR) AF: 0.146 AC: 2951 AN: 20264

American (AMR) AF: 0.344 AC: 12122 AN: 35288

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 5286 AN: 21308

East Asian (EAS) AF: 0.453 AC: 15053 AN: 33262

South Asian (SAS) AF: 0.188 AC: 12778 AN: 68034

European-Finnish (FIN) AF: 0.273 AC: 9763 AN: 35820

Middle Eastern (MID) AF: 0.275 AC: 792 AN: 2882

European-Non Finnish (NFE) AF: 0.224 AC: 118847 AN: 530342

Other (OTH) AF: 0.236 AC: 9006 AN: 38102

GnomAD4 genome AF: 0.217 AC: 33072 AN: 152070 Hom.: 3836 Cov.: 32 AF XY: 0.219 AC XY: 16284 AN XY: 74332

African (AFR) AF: 0.152 AC: 6296 AN: 41484

American (AMR) AF: 0.270 AC: 4131 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 850 AN: 3472

East Asian (EAS) AF: 0.395 AC: 2041 AN: 5170

South Asian (SAS) AF: 0.176 AC: 849 AN: 4820

European-Finnish (FIN) AF: 0.265 AC: 2797 AN: 10544

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.224 AC: 15236 AN: 67972

Other (OTH) AF: 0.230 AC: 486 AN: 2112

Alfa AF: 0.226 Hom.: 7275

Bravo AF: 0.221

Asia WGS AF: 0.285 AC: 991 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.6
DANN	Benign	0.51
PhyloP100		-0.050
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: rs3136558; hg19: chr2-113591275;