chr2-112836810-G-A

Variant names:

• chr2-112836810-G-A
• rs1143627
• ENST00000418817.5:c.-146C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: -0.268
• Publications: 719 publications found

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)

ENSG00000299339 (HGNC:):

ACMG classification

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	c.-118C>T		upstream_gene_variant		ENST00000263341.7	NP_000567.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.556 AC: 84516 AN: 151922 Hom.: 24620 Cov.: 32

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.: 0 AF XY: 0.614 AC XY: 387 AN XY: 630

African (AFR) AF: 0.250 AC: 1 AN: 4

American (AMR) AF: 0.489 AC: 133 AN: 272

Ashkenazi Jewish (ASJ) AF: 0.833 AC: 5 AN: 6

East Asian (EAS) AF: 0.667 AC: 12 AN: 18

South Asian (SAS) AF: 0.397 AC: 50 AN: 126

European-Finnish (FIN) AF: 0.750 AC: 3 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.708 AC: 525 AN: 742

Other (OTH) AF: 0.655 AC: 38 AN: 58

GnomAD4 genome AF: 0.556 AC: 84513 AN: 152040 Hom.: 24616 Cov.: 32 AF XY: 0.549 AC XY: 40793 AN XY: 74300

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

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

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	11
DANN	Benign	0.91
PhyloP100		-0.27
PromoterAI		0.26	Neutral
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

Other links and lift over

dbSNP: rs1143627; hg19: chr2-113594387;