rs5744280

chr11-112145791-G-A

Variant summary

Our verdict is Benign. Variant got -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

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 -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 id 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/exons	MANE	UniProt
IL18	NM_001562.4	c.361-1974C>T		intron_variant		ENST00000280357.12
IL18	NM_001243211.2	c.349-1974C>T		intron_variant
IL18	NM_001386420.1	c.361-1974C>T		intron_variant
IL18	XM_011542805.2	c.349-1974C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL18	ENST00000280357.12	c.361-1974C>T		intron_variant		1	NM_001562.4	P3

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

Gnomad4 AFR AF: 0.354

Gnomad4 AMR AF: 0.361

Gnomad4 ASJ AF: 0.364

Gnomad4 EAS AF: 0.445

Gnomad4 SAS AF: 0.569

Gnomad4 FIN AF: 0.282

Gnomad4 NFE AF: 0.330

Gnomad4 OTH AF: 0.377

Alfa AF: 0.339 Hom.: 4350

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

Benign, no assertion criteria provided

clinical testing

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	4.5
Dann	Benign	0.72

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: rs5744280; hg19: chr11-112016514;