rs4988359

chr11-112155192-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.-8-131A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 540,982 control chromosomes in the GnomAD database, including 11,406 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 0.16 (2699 hom., cov: 32)
  • Exomes 𝑓: 0.19 (8707 hom.)
• Consequence: IL18 NM_001562.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0220

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL18	NM_001562.4	c.-8-131A>G		intron_variant		ENST00000280357.12
IL18	NM_001243211.2	c.-8-131A>G		intron_variant
IL18	NM_001386420.1	c.-29-110A>G		intron_variant
IL18	XM_011542805.2	c.-29-110A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL18	ENST00000280357.12	c.-8-131A>G		intron_variant		1	NM_001562.4	P3

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24721 AN: 152076 Hom.: 2698 Cov.: 32

Gnomad AFR AF: 0.0454

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.00538

Gnomad SAS AF: 0.0820

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.158

GnomAD4 exome AF: 0.192 AC: 74655 AN: 388788 Hom.: 8707 AF XY: 0.188 AC XY: 38112 AN XY: 202654

Gnomad4 AFR exome AF: 0.0416

Gnomad4 AMR exome AF: 0.130

Gnomad4 ASJ exome AF: 0.126

Gnomad4 EAS exome AF: 0.00658

Gnomad4 SAS exome AF: 0.0776

Gnomad4 FIN exome AF: 0.236

Gnomad4 NFE exome AF: 0.242

Gnomad4 OTH exome AF: 0.183

GnomAD4 genome AF: 0.162 AC: 24720 AN: 152194 Hom.: 2699 Cov.: 32 AF XY: 0.158 AC XY: 11771 AN XY: 74406

Gnomad4 AFR AF: 0.0453

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.125

Gnomad4 EAS AF: 0.00520

Gnomad4 SAS AF: 0.0825

Gnomad4 FIN AF: 0.234

Gnomad4 NFE AF: 0.246

Gnomad4 OTH AF: 0.155

Alfa AF: 0.215 Hom.: 779

Bravo AF: 0.153

Asia WGS AF: 0.0390 AC: 136 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	7.2
Dann	Benign	0.80

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: rs4988359; hg19: chr11-112025915;