NM_001562.4:c.-8-132C>G

Variant names:

• chr11-112155193-G-C
• rs360721
• NM_001562.4:c.-8-132C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001562.4(IL18):​c.-8-132C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 533,580 control chromosomes in the GnomAD database, including 22,095 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 0.28 (6017 hom., cov: 32)
  • Exomes 𝑓: 0.28 (16078 hom.)
• Consequence: IL18 NM_001562.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.00
• Publications: 31 publications found

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]

ENSG00000255292 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001562.4. 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
	IL18	NM_001562.4	MANE Select	c.-8-132C>G		intron	N/A	NP_001553.1
	IL18	NM_001386420.1		c.-29-111C>G		intron	N/A	NP_001373349.1
	IL18	NM_001243211.2		c.-8-132C>G		intron	N/A	NP_001230140.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL18	ENST00000280357.12	TSL:1 MANE Select	c.-8-132C>G		intron	N/A	ENSP00000280357.7
	IL18	ENST00000524595.6	TSL:1	c.-8-132C>G		intron	N/A	ENSP00000434561.1
	ENSG00000255292	ENST00000532699.1	TSL:3	n.315-15226G>C		intron	N/A	ENSP00000456434.1

Frequencies

GnomAD3 genomes AF: 0.276 AC: 41913 AN: 151878 Hom.: 6019 Cov.: 32

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.272

GnomAD4 exome AF: 0.284 AC: 108198 AN: 381584 Hom.: 16078 AF XY: 0.282 AC XY: 56102 AN XY: 198726

African (AFR) AF: 0.213 AC: 2479 AN: 11624

American (AMR) AF: 0.334 AC: 5341 AN: 16010

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 3464 AN: 12114

East Asian (EAS) AF: 0.124 AC: 3727 AN: 29972

South Asian (SAS) AF: 0.241 AC: 6734 AN: 27958

European-Finnish (FIN) AF: 0.311 AC: 9678 AN: 31094

Middle Eastern (MID) AF: 0.242 AC: 567 AN: 2342

European-Non Finnish (NFE) AF: 0.306 AC: 69746 AN: 227702

Other (OTH) AF: 0.284 AC: 6462 AN: 22768

GnomAD4 genome AF: 0.276 AC: 41903 AN: 151996 Hom.: 6017 Cov.: 32 AF XY: 0.275 AC XY: 20450 AN XY: 74266

African (AFR) AF: 0.217 AC: 9014 AN: 41464

American (AMR) AF: 0.322 AC: 4919 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 1018 AN: 3468

East Asian (EAS) AF: 0.127 AC: 659 AN: 5170

South Asian (SAS) AF: 0.229 AC: 1106 AN: 4824

European-Finnish (FIN) AF: 0.313 AC: 3287 AN: 10516

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.309 AC: 21034 AN: 67974

Other (OTH) AF: 0.269 AC: 567 AN: 2110

Alfa AF: 0.166 Hom.: 339

Bravo AF: 0.275

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.6
DANN	Benign	0.61
PhyloP100		1.0
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: rs360721; hg19: chr11-112025916; COSMIC: COSV54781158; COSMIC: COSV54781158;