rs5744241

Variant names:

• chr11-112156421-T-C
• rs5744241
• NM_001562.4:c.-8-1360A>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.-8-1360A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0611 in 152,228 control chromosomes in the GnomAD database, including 409 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 0.061 (409 hom., cov: 32)
• Consequence: IL18 NM_001562.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.52
• Publications: 5 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0898 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.-8-1360A>G		intron	N/A	NP_001553.1
	IL18	NM_001386420.1		c.-29-1339A>G		intron	N/A	NP_001373349.1
	IL18	NM_001243211.2		c.-8-1360A>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.-8-1360A>G		intron	N/A	ENSP00000280357.7
	IL18	ENST00000524595.6	TSL:1	c.-8-1360A>G		intron	N/A	ENSP00000434561.1
	ENSG00000255292	ENST00000532699.1	TSL:3	n.315-13998T>C		intron	N/A	ENSP00000456434.1

Frequencies

GnomAD3 genomes AF: 0.0612 AC: 9308 AN: 152110 Hom.: 409 Cov.: 32

Gnomad AFR AF: 0.0169

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.0437

Gnomad ASJ AF: 0.0259

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0143

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0917

Gnomad OTH AF: 0.0541

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0611 AC: 9305 AN: 152228 Hom.: 409 Cov.: 32 AF XY: 0.0607 AC XY: 4520 AN XY: 74422

African (AFR) AF: 0.0169 AC: 702 AN: 41548

American (AMR) AF: 0.0436 AC: 666 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0259 AC: 90 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5182

South Asian (SAS) AF: 0.0143 AC: 69 AN: 4828

European-Finnish (FIN) AF: 0.123 AC: 1300 AN: 10588

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0917 AC: 6235 AN: 68008

Other (OTH) AF: 0.0530 AC: 112 AN: 2112

Alfa AF: 0.0709 Hom.: 66

Bravo AF: 0.0551

Asia WGS AF: 0.00722 AC: 25 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.8
DANN	Benign	0.64
PhyloP100		1.5
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: rs5744241; hg19: chr11-112027144;