2-112835941-G-A

Position:

• chr2-112835941-G-A

Variant summary

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

The NM_000576.3(IL1B):​c.47+242C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.599 in 152,056 control chromosomes in the GnomAD database, including 27,832 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 0.60 (27832 hom., cov: 32)
• Consequence: IL1B NM_000576.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.134

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL1B	NM_000576.3	c.47+242C>T		intron_variant		ENST00000263341.7	NP_000567.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL1B	ENST00000263341.7	c.47+242C>T		intron_variant		1	NM_000576.3	ENSP00000263341	P1

Frequencies

GnomAD3 genomes AF: 0.600 AC: 91104 AN: 151938 Hom.: 27811 Cov.: 32

Gnomad AFR AF: 0.551

Gnomad AMI AF: 0.736

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.652

Gnomad EAS AF: 0.529

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.597

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.666

Gnomad OTH AF: 0.609

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

GnomAD4 genome AF: 0.599 AC: 91154 AN: 152056 Hom.: 27832 Cov.: 32 AF XY: 0.591 AC XY: 43878 AN XY: 74296

Gnomad4 AFR AF: 0.551

Gnomad4 AMR AF: 0.507

Gnomad4 ASJ AF: 0.652

Gnomad4 EAS AF: 0.530

Gnomad4 SAS AF: 0.388

Gnomad4 FIN AF: 0.597

Gnomad4 NFE AF: 0.666

Gnomad4 OTH AF: 0.602

Alfa AF: 0.618 Hom.: 4457

Bravo AF: 0.595

Asia WGS AF: 0.449 AC: 1563 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	1.8
DANN	Benign	0.57

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

Publications

LitVar

Other links and lift over

dbSNP: rs1143629; hg19: chr2-113593518;