rs5744280

Variant names:

• chr11-112145791-G-A
• rs5744280
• NM_001562.4:c.361-1974C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_001562.4(IL18):​c.361-1974C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 151,896 control chromosomes in the GnomAD database, including 9,427 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency: Genomes: 𝑓 0.35 (9427 hom., cov: 32)
• Consequence: IL18 NM_001562.4 intron
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.505
• Publications: 22 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 11-112145791-G-A is Benign according to our data. Variant chr11-112145791-G-A is described in ClinVar as Benign. ClinVar VariationId is 812622.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL18	NM_001562.4	c.361-1974C>T		intron_variant	Intron 5 of 5	ENST00000280357.12	NP_001553.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL18	ENST00000280357.12	c.361-1974C>T		intron_variant	Intron 5 of 5	1	NM_001562.4	ENSP00000280357.7
ENSG00000255292	ENST00000532699.1	n.315-24628G>A		intron_variant	Intron 3 of 5	3		ENSP00000456434.1

Frequencies

GnomAD3 genomes AF: 0.349 AC: 52976 AN: 151778 Hom.: 9407 Cov.: 32

Gnomad AFR AF: 0.355

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.445

Gnomad SAS AF: 0.568

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.330

Gnomad OTH AF: 0.371

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

GnomAD4 genome AF: 0.349 AC: 53027 AN: 151896 Hom.: 9427 Cov.: 32 AF XY: 0.352 AC XY: 26156 AN XY: 74220

African (AFR) AF: 0.354 AC: 14660 AN: 41370

American (AMR) AF: 0.361 AC: 5510 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.364 AC: 1264 AN: 3472

East Asian (EAS) AF: 0.445 AC: 2299 AN: 5166

South Asian (SAS) AF: 0.569 AC: 2745 AN: 4824

European-Finnish (FIN) AF: 0.282 AC: 2972 AN: 10524

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.330 AC: 22410 AN: 67956

Other (OTH) AF: 0.377 AC: 795 AN: 2108

Alfa AF: 0.339 Hom.: 6281

Bravo AF: 0.350

Asia WGS AF: 0.507 AC: 1764 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

Three Vessel Coronary Disease Benign:1

Department of Cardiology, Chinese Academy of Medical Sciences, Fuwai Hospital

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.5
DANN	Benign	0.72
PhyloP100		0.51
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: rs5744280; hg19: chr11-112016514;