2-112830541-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.517

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 -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 GnomAd at 83 AD gene.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.000719 AC: 83 AN: 115420 Hom.: 0 Cov.: 30

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.: 0 AF XY: 0.000454 AC XY: 58 AN XY: 127722

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.: 1 Cov.: 31 AF XY: 0.000831 AC XY: 583 AN XY: 701482

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: 83 AN: 115420 Hom.: 0 Cov.: 30 AF XY: 0.000491 AC XY: 28 AN XY: 57040

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.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2020

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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

Other links and lift over

dbSNP: rs138009692; hg19: chr2-113588118; COSMIC: COSV54522122; COSMIC: COSV54522122;