Variant 2-112830541-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_000576.3(IL1B):c.630G>A(p.Lys210=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000837 in 1,526,932 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00072 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00085 ( 1 hom. )

Consequence

IL1B
NM_000576.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.517

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 2-112830541-C-T is Benign according to our data. Variant chr2-112830541-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 916339.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.517 with no splicing effect.

BS2

High AC in GnomAd4 at 83 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1B	NM_000576.3 linkuse as main transcript	c.630G>A	p.Lys210=	synonymous_variant	7/7	ENST00000263341.7
IL1B	XM_047444175.1 linkuse as main transcript	c.396G>A	p.Lys132=	synonymous_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1B	ENST00000263341.7 linkuse as main transcript	c.630G>A	p.Lys210=	synonymous_variant	7/7	1	NM_000576.3	P1
IL1B	ENST00000491056.5 linkuse as main transcript	n.1437G>A		non_coding_transcript_exon_variant	6/6	1

Frequencies

GnomAD3 genomes

AF:

0.000719

AC:

AN:

115420

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000263

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000256

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00136

Gnomad OTH

AF:

0.00134

GnomAD3 exomes

AF:

0.000500

AC:

118

AN:

235810

Hom.:

AF XY:

0.000454

AC XY:

AN XY:

127722

show subpopulations

Gnomad AFR exome

AF:

0.000136

Gnomad AMR exome

AF:

0.000781

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000352

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000795

Gnomad OTH exome

AF:

0.000710

GnomAD4 exome

AF:

0.000847

AC:

1195

AN:

1411512

Hom.:

Cov.:

AF XY:

0.000831

AC XY:

583

AN XY:

701482

show subpopulations

Gnomad4 AFR exome

AF:

0.000285

Gnomad4 AMR exome

AF:

0.000762

Gnomad4 ASJ exome

AF:

0.0000404

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000509

Gnomad4 FIN exome

AF:

0.0000386

Gnomad4 NFE exome

AF:

0.00102

Gnomad4 OTH exome

AF:

0.000762

GnomAD4 genome

AF:

0.000719

AC:

AN:

115420

Hom.:

Cov.:

AF XY:

0.000491

AC XY:

AN XY:

57040

show subpopulations

Gnomad4 AFR

AF:

0.000263

Gnomad4 AMR

AF:

0.000256

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00136

Gnomad4 OTH

AF:

0.00134

Alfa

AF:

0.000647

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

6.8

DANN

Benign

0.66

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