Variant chr2-112832890-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000263341.7(IL1B):c.302-64G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 1,568,952 control chromosomes in the GnomAD database, including 95,129 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 0.31 ( 7669 hom., cov: 32)

Exomes 𝑓: 0.35 ( 87460 hom. )

Consequence

IL1B
ENST00000263341.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.479

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=-0.81).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL1B	NM_000576.3 linkuse as main transcript	c.302-64G>A		intron_variant		ENST00000263341.7	NP_000567.1
IL1B	XM_047444175.1 linkuse as main transcript	c.68-64G>A		intron_variant			XP_047300131.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL1B	ENST00000263341.7 linkuse as main transcript	c.302-64G>A		intron_variant		1	NM_000576.3	ENSP00000263341	P1

Frequencies

GnomAD3 genomes

AF:

0.306

AC:

46546

AN:

151916

Hom.:

7670

Cov.:

show subpopulations

Gnomad AFR

AF:

0.209

Gnomad AMI

AF:

0.323

Gnomad AMR

AF:

0.288

Gnomad ASJ

AF:

0.332

Gnomad EAS

AF:

0.564

Gnomad SAS

AF:

0.254

Gnomad FIN

AF:

0.268

Gnomad MID

AF:

0.264

Gnomad NFE

AF:

0.358

Gnomad OTH

AF:

0.318

GnomAD4 exome

AF:

0.347

AC:

491220

AN:

1416918

Hom.:

87460

Cov.:

AF XY:

0.344

AC XY:

243579

AN XY:

707454

show subpopulations

Gnomad4 AFR exome

AF:

0.200

Gnomad4 AMR exome

AF:

0.295

Gnomad4 ASJ exome

AF:

0.337

Gnomad4 EAS exome

AF:

0.574

Gnomad4 SAS exome

AF:

0.245

Gnomad4 FIN exome

AF:

0.280

Gnomad4 NFE exome

AF:

0.357

Gnomad4 OTH exome

AF:

0.343

GnomAD4 genome

AF:

0.306

AC:

46563

AN:

152034

Hom.:

7669

Cov.:

AF XY:

0.303

AC XY:

22515

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.209

Gnomad4 AMR

AF:

0.288

Gnomad4 ASJ

AF:

0.332

Gnomad4 EAS

AF:

0.565

Gnomad4 SAS

AF:

0.254

Gnomad4 FIN

AF:

0.268

Gnomad4 NFE

AF:

0.358

Gnomad4 OTH

AF:

0.313

Alfa

AF:

0.350

Hom.:

16224

Bravo

AF:

0.308

Asia WGS

AF:

0.339

AC:

1180

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.5

DANN

Benign

0.55

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over