rs1143639

Variant names:

• chr2-112831216-C-T
• rs1143639
• NM_000576.3:c.597+76G>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.597+76G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 1,546,724 control chromosomes in the GnomAD database, including 39,101 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 0.20 (3135 hom., cov: 31)
  • Exomes 𝑓: 0.22 (35966 hom.)
• Consequence: IL1B NM_000576.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.899
• Publications: 14 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1B	NM_000576.3	c.597+76G>A		intron_variant	Intron 6 of 6	ENST00000263341.7	NP_000567.1
IL1B	XM_047444175.1	c.363+76G>A		intron_variant	Intron 3 of 3		XP_047300131.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1B	ENST00000263341.7	c.597+76G>A		intron_variant	Intron 6 of 6	1	NM_000576.3	ENSP00000263341.2

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29729 AN: 151820 Hom.: 3130 Cov.: 31

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.318

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.0217

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.210

GnomAD4 exome AF: 0.221 AC: 307607 AN: 1394784 Hom.: 35966 Cov.: 21 AF XY: 0.221 AC XY: 153786 AN XY: 697348

African (AFR) AF: 0.142 AC: 4593 AN: 32242

American (AMR) AF: 0.118 AC: 5233 AN: 44510

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 7107 AN: 25554

East Asian (EAS) AF: 0.0333 AC: 1303 AN: 39186

South Asian (SAS) AF: 0.168 AC: 14225 AN: 84468

European-Finnish (FIN) AF: 0.251 AC: 13218 AN: 52730

Middle Eastern (MID) AF: 0.316 AC: 1752 AN: 5552

European-Non Finnish (NFE) AF: 0.235 AC: 247792 AN: 1052570

Other (OTH) AF: 0.214 AC: 12384 AN: 57972

GnomAD4 genome AF: 0.196 AC: 29747 AN: 151940 Hom.: 3135 Cov.: 31 AF XY: 0.195 AC XY: 14456 AN XY: 74266

African (AFR) AF: 0.143 AC: 5924 AN: 41414

American (AMR) AF: 0.172 AC: 2621 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 952 AN: 3470

East Asian (EAS) AF: 0.0220 AC: 114 AN: 5186

South Asian (SAS) AF: 0.153 AC: 738 AN: 4820

European-Finnish (FIN) AF: 0.248 AC: 2622 AN: 10552

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.235 AC: 15942 AN: 67944

Other (OTH) AF: 0.209 AC: 441 AN: 2110

Alfa AF: 0.232 Hom.: 1521

Bravo AF: 0.186

Asia WGS AF: 0.115 AC: 400 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.21
DANN	Benign	0.59
PhyloP100		-0.90
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: rs1143639; hg19: chr2-113588793; COSMIC: COSV54521174; COSMIC: COSV54521174;