2-112836810-G-A

Position:

• chr2-112836810-G-A

Variant summary

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

The ENST00000418817.5(IL1B):​c.-146C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 153,270 control chromosomes in the GnomAD database, including 24,871 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

• Frequency:
  • Genomes: 𝑓 0.56 (24616 hom., cov: 32)
  • Exomes 𝑓: 0.62 (255 hom.)
• Consequence: IL1B ENST00000418817.5 5_prime_UTR
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: -0.268

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=-0.56).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.66 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL1B	NM_000576.3			upstream_gene_variant		ENST00000263341.7	NP_000567.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL1B	ENST00000263341.7			upstream_gene_variant		1	NM_000576.3	ENSP00000263341	P1

Frequencies

GnomAD3 genomes AF: 0.556 AC: 84516 AN: 151922 Hom.: 24620 Cov.: 32

Gnomad AFR AF: 0.397

Gnomad AMI AF: 0.736

Gnomad AMR AF: 0.495

Gnomad ASJ AF: 0.652

Gnomad EAS AF: 0.530

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.597

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.665

Gnomad OTH AF: 0.575

GnomAD4 exome AF: 0.624 AC: 767 AN: 1230 Hom.: 255 Cov.: 0 AF XY: 0.614 AC XY: 387 AN XY: 630

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.489

Gnomad4 ASJ exome AF: 0.833

Gnomad4 EAS exome AF: 0.667

Gnomad4 SAS exome AF: 0.397

Gnomad4 FIN exome AF: 0.750

Gnomad4 NFE exome AF: 0.708

Gnomad4 OTH exome AF: 0.655

GnomAD4 genome AF: 0.556 AC: 84513 AN: 152040 Hom.: 24616 Cov.: 32 AF XY: 0.549 AC XY: 40793 AN XY: 74300

Gnomad4 AFR AF: 0.396

Gnomad4 AMR AF: 0.494

Gnomad4 ASJ AF: 0.652

Gnomad4 EAS AF: 0.530

Gnomad4 SAS AF: 0.404

Gnomad4 FIN AF: 0.597

Gnomad4 NFE AF: 0.665

Gnomad4 OTH AF: 0.569

Alfa AF: 0.641 Hom.: 61214

Bravo AF: 0.544

Asia WGS AF: 0.443 AC: 1539 AN: 3478

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Gastric cancer susceptibility after h. pylori infection Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Nov 04, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	11
DANN	Benign	0.91

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: rs1143627; hg19: chr2-113594387;