rs16062

chr2-112833504-G-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_000576.3(IL1B):c.171C>T(p.Tyr57=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00224 in 1,614,238 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0015 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (5 hom.)
• Consequence: IL1B NM_000576.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.355

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 2-112833504-G-A is Benign according to our data. Variant chr2-112833504-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 779077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.355 with no splicing effect.
• BS2: High AC in GnomAd at 228 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1B	NM_000576.3	c.171C>T	p.Tyr57=	synonymous_variant	4/7	ENST00000263341.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1B	ENST00000263341.7	c.171C>T	p.Tyr57=	synonymous_variant	4/7	1	NM_000576.3	P1

Frequencies

GnomAD3 genomes AF: 0.00150 AC: 228 AN: 152242 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000785

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000847

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00250

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00117 AC: 293 AN: 251456 Hom.: 0 AF XY: 0.00121 AC XY: 164 AN XY: 135906

Gnomad AFR exome AF: 0.000861

Gnomad AMR exome AF: 0.000491

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.000462

Gnomad NFE exome AF: 0.00213

Gnomad OTH exome AF: 0.000977

GnomAD4 exome AF: 0.00232 AC: 3388 AN: 1461878 Hom.: 5 Cov.: 32 AF XY: 0.00220 AC XY: 1602 AN XY: 727240

Gnomad4 AFR exome AF: 0.000717

Gnomad4 AMR exome AF: 0.000447

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000128

Gnomad4 FIN exome AF: 0.000524

Gnomad4 NFE exome AF: 0.00287

Gnomad4 OTH exome AF: 0.00189

GnomAD4 genome AF: 0.00150 AC: 228 AN: 152360 Hom.: 0 Cov.: 32 AF XY: 0.00129 AC XY: 96 AN XY: 74514

Gnomad4 AFR AF: 0.000721

Gnomad4 AMR AF: 0.000784

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.000847

Gnomad4 NFE AF: 0.00250

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00134 Hom.: 0

Bravo AF: 0.00125

EpiCase AF: 0.00207

EpiControl AF: 0.00207

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	May 01, 2022	IL1B: BP4, BP7 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jul 11, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.91
Dann	Benign	0.71

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: rs16062; hg19: chr2-113591081;