rs2853550

Variant names:

• chr2-112829544-A-G
• rs2853550
• NM_000576.3:c.*817T>C

Your query was ambiguous. Multiple possible variants found:

• chr2-112829544-A-G
• chr2-112829544-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000576.3(IL1B):​c.*817T>C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.837 in 152,062 control chromosomes in the GnomAD database, including 54,266 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 0.84 (54266 hom., cov: 30)
• Consequence: IL1B NM_000576.3 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.281

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.914 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1B	NM_000576.3	c.*817T>C		downstream_gene_variant		ENST00000263341.7	NP_000567.1
IL1B	XM_047444175.1	c.*817T>C		downstream_gene_variant			XP_047300131.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1B	ENST00000263341.7	c.*817T>C		downstream_gene_variant		1	NM_000576.3	ENSP00000263341.2

Frequencies

GnomAD3 genomes AF: 0.837 AC: 127235 AN: 151944 Hom.: 54226 Cov.: 30

Gnomad AFR AF: 0.664

Gnomad AMI AF: 0.962

Gnomad AMR AF: 0.838

Gnomad ASJ AF: 0.894

Gnomad EAS AF: 0.915

Gnomad SAS AF: 0.777

Gnomad FIN AF: 0.939

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.920

Gnomad OTH AF: 0.849

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

GnomAD4 genome AF: 0.837 AC: 127322 AN: 152062 Hom.: 54266 Cov.: 30 AF XY: 0.838 AC XY: 62306 AN XY: 74356

Gnomad4 AFR AF: 0.664

Gnomad4 AMR AF: 0.838

Gnomad4 ASJ AF: 0.894

Gnomad4 EAS AF: 0.916

Gnomad4 SAS AF: 0.777

Gnomad4 FIN AF: 0.939

Gnomad4 NFE AF: 0.920

Gnomad4 OTH AF: 0.850

Alfa AF: 0.896 Hom.: 59892

Bravo AF: 0.824

Asia WGS AF: 0.834 AC: 2899 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.2
DANN	Benign	0.82

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2853550; hg19: chr2-113587121;