chr11-112164016-A-C

Position:

• chr11-112164016-A-C

Variant summary

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

The ENST00000280357.12(IL18):​c.-119T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 152,320 control chromosomes in the GnomAD database, including 5,162 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 0.26 (5156 hom., cov: 33)
  • Exomes 𝑓: 0.29 (6 hom.)
• Consequence: IL18 ENST00000280357.12 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.540

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL18	NM_001562.4	c.-119T>G		5_prime_UTR_variant	1/6	ENST00000280357.12	NP_001553.1
IL18	NM_001243211.2	c.-119T>G		5_prime_UTR_variant	1/5		NP_001230140.1
IL18	NM_001386420.1	c.-140T>G		5_prime_UTR_variant	1/6		NP_001373349.1
IL18	XM_011542805.2	c.-140T>G		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.-119T>G		5_prime_UTR_variant	1/6	1	NM_001562.4	ENSP00000280357	P3

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38910 AN: 151982 Hom.: 5157 Cov.: 33

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.254

GnomAD4 exome AF: 0.286 AC: 63 AN: 220 Hom.: 6 Cov.: 0 AF XY: 0.282 AC XY: 40 AN XY: 142

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.286

Gnomad4 SAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.280

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.256 AC: 38902 AN: 152100 Hom.: 5156 Cov.: 33 AF XY: 0.256 AC XY: 19013 AN XY: 74358

Gnomad4 AFR AF: 0.225

Gnomad4 AMR AF: 0.300

Gnomad4 ASJ AF: 0.267

Gnomad4 EAS AF: 0.128

Gnomad4 SAS AF: 0.214

Gnomad4 FIN AF: 0.286

Gnomad4 NFE AF: 0.272

Gnomad4 OTH AF: 0.251

Alfa AF: 0.265 Hom.: 2171

Bravo AF: 0.257

Asia WGS AF: 0.186 AC: 649 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.8
DANN	Benign	0.54
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: rs360718; hg19: chr11-112034739;