chr2-112835315-GA-G

Variant names:

• chr2-112835315-GA-G
• rs3917354
• NM_000576.3:c.99+250delT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_000576.3(IL1B):​c.99+250delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 559,934 control chromosomes in the GnomAD database, including 9,795 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.16 (2226 hom., cov: 29)
  • Exomes 𝑓: 0.18 (7569 hom.)
• Consequence: IL1B NM_000576.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00400
• Publications: 5 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000576.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1B	NM_000576.3	MANE Select	c.99+250delT		intron	N/A	NP_000567.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1B	ENST00000263341.7	TSL:1 MANE Select	c.99+250delT		intron	N/A	ENSP00000263341.2
	IL1B	ENST00000491056.5	TSL:1	n.649+250delT		intron	N/A
	IL1B	ENST00000477398.1	TSL:2	n.436delT		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24256 AN: 152038 Hom.: 2225 Cov.: 29

Gnomad AFR AF: 0.0810

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.0437

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.173

GnomAD4 exome AF: 0.183 AC: 74739 AN: 407778 Hom.: 7569 Cov.: 0 AF XY: 0.182 AC XY: 39329 AN XY: 215792

African (AFR) AF: 0.0820 AC: 943 AN: 11504

American (AMR) AF: 0.114 AC: 2007 AN: 17680

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 3040 AN: 12338

East Asian (EAS) AF: 0.0469 AC: 1270 AN: 27106

South Asian (SAS) AF: 0.141 AC: 6308 AN: 44750

European-Finnish (FIN) AF: 0.214 AC: 5639 AN: 26354

Middle Eastern (MID) AF: 0.262 AC: 534 AN: 2036

European-Non Finnish (NFE) AF: 0.209 AC: 50591 AN: 242586

Other (OTH) AF: 0.188 AC: 4407 AN: 23424

GnomAD4 genome AF: 0.159 AC: 24255 AN: 152156 Hom.: 2226 Cov.: 29 AF XY: 0.157 AC XY: 11645 AN XY: 74374

African (AFR) AF: 0.0809 AC: 3359 AN: 41502

American (AMR) AF: 0.140 AC: 2138 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 874 AN: 3470

East Asian (EAS) AF: 0.0436 AC: 226 AN: 5180

South Asian (SAS) AF: 0.127 AC: 614 AN: 4826

European-Finnish (FIN) AF: 0.206 AC: 2177 AN: 10586

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.208 AC: 14133 AN: 67990

Other (OTH) AF: 0.173 AC: 364 AN: 2110

Alfa AF: 0.184 Hom.: 344

Bravo AF: 0.150

Asia WGS AF: 0.107 AC: 369 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.0040
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: rs3917354; hg19: chr2-113592892;