rs1071676

Variant names:

• chr2-112829856-C-G
• rs1071676
• NM_000576.3:c.*505G>C

Variant summary

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

The NM_000576.3(IL1B):​c.*505G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 155,964 control chromosomes in the GnomAD database, including 3,233 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.20 (3151 hom., cov: 32)
  • Exomes 𝑓: 0.18 (82 hom.)
• Consequence: IL1B NM_000576.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.493
• Publications: 40 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1B	NM_000576.3	c.*505G>C		3_prime_UTR_variant	Exon 7 of 7	ENST00000263341.7	NP_000567.1
IL1B	XM_047444175.1	c.*505G>C		3_prime_UTR_variant	Exon 4 of 4		XP_047300131.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1B	ENST00000263341.7	c.*505G>C		3_prime_UTR_variant	Exon 7 of 7	1	NM_000576.3	ENSP00000263341.2

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29823 AN: 151920 Hom.: 3146 Cov.: 32

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.0221

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.211

GnomAD4 exome AF: 0.182 AC: 715 AN: 3926 Hom.: 82 Cov.: 0 AF XY: 0.185 AC XY: 384 AN XY: 2076

African (AFR) AF: 0.0625 AC: 1 AN: 16

American (AMR) AF: 0.120 AC: 110 AN: 918

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 4 AN: 14

East Asian (EAS) AF: 0.00926 AC: 1 AN: 108

South Asian (SAS) AF: 0.123 AC: 57 AN: 462

European-Finnish (FIN) AF: 0.0833 AC: 2 AN: 24

Middle Eastern (MID) AF: 1.00 AC: 2 AN: 2

European-Non Finnish (NFE) AF: 0.227 AC: 511 AN: 2250

Other (OTH) AF: 0.205 AC: 27 AN: 132

GnomAD4 genome AF: 0.196 AC: 29840 AN: 152038 Hom.: 3151 Cov.: 32 AF XY: 0.195 AC XY: 14501 AN XY: 74330

African (AFR) AF: 0.143 AC: 5944 AN: 41450

American (AMR) AF: 0.174 AC: 2655 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.275 AC: 953 AN: 3470

East Asian (EAS) AF: 0.0224 AC: 116 AN: 5182

South Asian (SAS) AF: 0.153 AC: 738 AN: 4818

European-Finnish (FIN) AF: 0.249 AC: 2625 AN: 10540

Middle Eastern (MID) AF: 0.356 AC: 104 AN: 292

European-Non Finnish (NFE) AF: 0.235 AC: 15969 AN: 67980

Other (OTH) AF: 0.211 AC: 445 AN: 2112

Alfa AF: 0.220 Hom.: 552

Bravo AF: 0.187

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.41
DANN	Benign	0.44
PhyloP100		-0.49
Mutation Taster		=100/0	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: rs1071676; hg19: chr2-113587433;