dbSNP rs1143627: IL1B:c.-146C>T (chr2-112836810-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
IL1B	NM_000576.3 link	c.-118C>T		upstream_gene_variant		ENST00000263341.7	NP_000567.1	P01584

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1B	ENST00000263341.7 link	c.-118C>T		upstream_gene_variant		1	NM_000576.3	ENSP00000263341.2		P01584

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

AC:

AN:

Gnomad4 AMR exome

AF:

0.489

AC:

133

AN:

272

Gnomad4 ASJ exome

AF:

0.833

AC:

AN:

Gnomad4 EAS exome

AF:

0.667

AC:

AN:

Gnomad4 SAS exome

AF:

0.397

AC:

AN:

126

Gnomad4 FIN exome

AF:

0.750

AC:

AN:

Gnomad4 NFE exome

AF:

0.708

AC:

525

AN:

742

Gnomad4 Remaining exome

AF:

0.655

AC:

AN:

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

AC:

0.396337

AN:

0.396337

Gnomad4 AMR

AF:

0.494

AC:

0.493847

AN:

0.493847

Gnomad4 ASJ

AF:

0.652

AC:

0.651585

AN:

0.651585

Gnomad4 EAS

AF:

0.530

AC:

0.529992

AN:

0.529992

Gnomad4 SAS

AF:

0.404

AC:

0.40399

AN:

0.40399

Gnomad4 FIN

AF:

0.597

AC:

0.596533

AN:

0.596533

Gnomad4 NFE

AF:

0.665

AC:

0.665255

AN:

0.665255

Gnomad4 OTH

AF:

0.569

AC:

0.569129

AN:

0.569129

Heterozygous variant carriers

1820

3640

5459

7279

9099

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

714

1428

2142

2856

3570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.628

Hom.:

134668

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

Nov 04, 2021

OMIM

Significance:risk factor

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.91

Mutation Taster

=300/0

polymorphism (auto)

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