Variant 2-112836810-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

risk factor no assertion criteria provided O:1

Conservation

PhyloP100: -0.268

Variant links:

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 links:

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ACMG classification

Classification made for transcript

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	UniProt
IL1B	NM_000576.3 linkuse as main transcript			upstream_gene_variant		ENST00000263341.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1B	ENST00000263341.7 linkuse as main transcript			upstream_gene_variant		1	NM_000576.3	P1

Frequencies

GnomAD3 genomes

AF:

0.556

AC:

84516

AN:

151922

Hom.:

24620

Cov.:

show subpopulations

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.:

AF XY:

0.614

AC XY:

387

AN XY:

630

show subpopulations

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.:

AF XY:

0.549

AC XY:

40793

AN XY:

74300

show subpopulations

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

LINK: link

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over