rs360717

Positions:

• chr11-112164002-G-A

Variant summary

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

The NM_001562.4(IL18):​c.-105C>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 0.252 in 152,274 control chromosomes in the GnomAD database, including 5,022 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 0.25 (5019 hom., cov: 33)
  • Exomes 𝑓: 0.25 (3 hom.)
• Consequence: IL18 NM_001562.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL18	NM_001562.4	c.-105C>T		5_prime_UTR_variant	1/6	ENST00000280357.12	NP_001553.1
IL18	NM_001243211.2	c.-105C>T		5_prime_UTR_variant	1/5		NP_001230140.1
IL18	NM_001386420.1	c.-126C>T		5_prime_UTR_variant	1/6		NP_001373349.1
IL18	XM_011542805.2	c.-126C>T		5_prime_UTR_variant	1/5		XP_011541107.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL18	ENST00000280357.12	c.-105C>T		5_prime_UTR_variant	1/6	1	NM_001562.4	ENSP00000280357	P3

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38295 AN: 151962 Hom.: 5020 Cov.: 33

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.251

GnomAD4 exome AF: 0.247 AC: 48 AN: 194 Hom.: 3 Cov.: 0 AF XY: 0.220 AC XY: 26 AN XY: 118

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 0.289

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.196

GnomAD4 genome AF: 0.252 AC: 38286 AN: 152080 Hom.: 5019 Cov.: 33 AF XY: 0.252 AC XY: 18721 AN XY: 74326

Gnomad4 AFR AF: 0.210

Gnomad4 AMR AF: 0.299

Gnomad4 ASJ AF: 0.267

Gnomad4 EAS AF: 0.128

Gnomad4 SAS AF: 0.214

Gnomad4 FIN AF: 0.287

Gnomad4 NFE AF: 0.272

Gnomad4 OTH AF: 0.248

Alfa AF: 0.266 Hom.: 9052

Bravo AF: 0.253

Asia WGS AF: 0.185 AC: 646 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.4
DANN	Benign	0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs360717; hg19: chr11-112034725;