chr2-112836810-G-A

Variant names:

Variant summary

Our verdict is The variant received -12 classification points (ACMG Germline Pathogenicity v2019). BA1BP4_Strong

The ENST00000418817.5(IL1B):c.-146C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Note: ENST00000418817.5 is not a MANE Select or MANE Plus Clinical transcript for IL1B; the reported annotation may differ from that of the MANE-designated reference transcript for this gene. The variant allele was found at a cumulative frequency of 0.556 (AC=85,280) in the gnomAD database across 153,270 control chromosomes, including 24,871 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.66. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain Significance (no review 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

Publications

735 publications found

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 Gene-Disease associations (from GenCC):

hereditary diffuse gastric adenocarcinoma
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

IL1B links:

ENSG00000299339 (HGNC:):

ENSG00000299339 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript ENST00000418817.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

Our verdict: Benign. The variant received -12 points.

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).

BA1

GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.6601 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: ENST00000418817.5. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1B	NM_000576.3	MANE Select	c.-118C>T		upstream_gene	N/A	NP_000567.1	P01584

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IL1B	ENST00000418817.5	TSL:3	c.-146C>T	5_prime_UTR	Exon 1 of 5	ENSP00000407219.1	C9JWV2
ENSG00000299339	ENST00000762706.1		n.405-48448G>A	intron	N/A
ENSG00000299339	ENST00000762707.1		n.500-48448G>A	intron	N/A

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

African (AFR)

AF:

0.250

AC:

AN:

American (AMR)

AF:

0.489

AC:

133

AN:

272

Ashkenazi Jewish (ASJ)

AF:

0.833

AC:

AN:

East Asian (EAS)

AF:

0.667

AC:

AN:

South Asian (SAS)

AF:

0.397

AC:

AN:

126

European-Finnish (FIN)

AF:

0.750

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.708

AC:

525

AN:

742

Other (OTH)

AF:

0.655

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

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

African (AFR)

AF:

0.396

AC:

16425

AN:

41442

American (AMR)

AF:

0.494

AC:

7544

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.652

AC:

2261

AN:

3470

East Asian (EAS)

AF:

0.530

AC:

2739

AN:

5168

South Asian (SAS)

AF:

0.404

AC:

1944

AN:

4812

European-Finnish (FIN)

AF:

0.597

AC:

6297

AN:

10556

Middle Eastern (MID)

AF:

0.660

AC:

194

AN:

294

European-Non Finnish (NFE)

AF:

0.665

AC:

45236

AN:

67998

Other (OTH)

AF:

0.569

AC:

1202

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1820

3640

5459

7279

9099

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

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

Local populations

ToMMo 61KJPN (+60KJPN MNV)

AF:

0.557

AC:

68319

AN:

122684

Turkish Variome

AF:

0.589

AC:

911

AN:

1546

Hom.:

277

WBBC (Westlake BioBank for Chinese) pilot

AF:

0.530

AC:

4751

AN:

8960

Hom.:

1280

ABraOM SABE-WGS-1171

AF:

0.573

AC:

1343

AN:

2342

Hom.:

385

ClinVar

ClinVar submissions

Significance:risk factor

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Gastric cancer susceptibility after h. pylori infection (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Benign

0.91

PhyloP100

-0.27

PromoterAI

0.26

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

Local populations

ClinVar

Computational scores

Splicing

Publications

Other links and lift over