11-112143366-T-C

Position:

• chr11-112143366-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001562.4(IL18):​c.*230A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.969 in 369,870 control chromosomes in the GnomAD database, including 173,790 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 0.96 (70112 hom., cov: 34)
  • Exomes 𝑓: 0.98 (103678 hom.)
• Consequence: IL18 NM_001562.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.39

Genes affected

IL18 (HGNC:5986): (interleukin 18) The protein encoded by this gene is a proinflammatory cytokine of the IL-1 family that is constitutively found as a precursor within the cytoplasm of a variety of cells including macrophages and keratinocytes. The inactive IL-18 precursor is processed to its active form by caspase-1, and is capable of stimulating interferon gamma production, and of regulating both T helper (Th) 1 and Th2 responses. This cytokine has been implicated in the injury of different organs, and in potentially fatal conditions characterized by a cytokine storm. In humans, IL-18 gene is located on chromosome 11. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Aug 2020]

IL18 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL18	NM_001562.4	c.*230A>G		3_prime_UTR_variant	6/6	ENST00000280357.12	NP_001553.1
IL18	NM_001386420.1	c.*230A>G		3_prime_UTR_variant	6/6		NP_001373349.1
IL18	NM_001243211.2	c.*230A>G		3_prime_UTR_variant	5/5		NP_001230140.1
IL18	XM_011542805.2	c.*230A>G		3_prime_UTR_variant	5/5		XP_011541107.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL18	ENST00000280357.12	c.*230A>G		3_prime_UTR_variant	6/6	1	NM_001562.4	ENSP00000280357.7
ENSG00000255292	ENST00000532699.1	n.315-27053T>C		intron_variant		3		ENSP00000456434.1

Frequencies

GnomAD3 genomes AF: 0.959 AC: 145937 AN: 152170 Hom.: 70070 Cov.: 34

Gnomad AFR AF: 0.906

Gnomad AMI AF: 0.992

Gnomad AMR AF: 0.972

Gnomad ASJ AF: 0.941

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.954

Gnomad FIN AF: 0.982

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.982

Gnomad OTH AF: 0.959

GnomAD4 exome AF: 0.976 AC: 212344 AN: 217582 Hom.: 103678 Cov.: 2 AF XY: 0.975 AC XY: 109913 AN XY: 112758

Gnomad4 AFR exome AF: 0.905

Gnomad4 AMR exome AF: 0.977

Gnomad4 ASJ exome AF: 0.940

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.948

Gnomad4 FIN exome AF: 0.984

Gnomad4 NFE exome AF: 0.982

Gnomad4 OTH exome AF: 0.972

GnomAD4 genome AF: 0.959 AC: 146038 AN: 152288 Hom.: 70112 Cov.: 34 AF XY: 0.960 AC XY: 71483 AN XY: 74460

Gnomad4 AFR AF: 0.906

Gnomad4 AMR AF: 0.972

Gnomad4 ASJ AF: 0.941

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.954

Gnomad4 FIN AF: 0.982

Gnomad4 NFE AF: 0.982

Gnomad4 OTH AF: 0.960

Alfa AF: 0.968 Hom.: 8860

Bravo AF: 0.957

Asia WGS AF: 0.971 AC: 3377 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.29
DANN	Benign	0.15

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

Other links and lift over

dbSNP: rs360727; hg19: chr11-112014089;