11-112155980-A-G

Position:

• chr11-112155980-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_001562.4(IL18):​c.-8-919T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.817 in 152,182 control chromosomes in the GnomAD database, including 51,456 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency: Genomes: 𝑓 0.82 (51456 hom., cov: 32)
• Consequence: IL18 NM_001562.4 intron
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.0190

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=-0.92).
• BP6: Variant 11-112155980-A-G is Benign according to our data. Variant chr11-112155980-A-G is described in ClinVar as [Benign]. Clinvar id is 812623.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.881 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL18	NM_001562.4	c.-8-919T>C		intron_variant		ENST00000280357.12	NP_001553.1
IL18	NM_001243211.2	c.-8-919T>C		intron_variant			NP_001230140.1
IL18	NM_001386420.1	c.-29-898T>C		intron_variant			NP_001373349.1
IL18	XM_011542805.2	c.-29-898T>C		intron_variant			XP_011541107.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL18	ENST00000280357.12	c.-8-919T>C		intron_variant		1	NM_001562.4	ENSP00000280357	P3

Frequencies

GnomAD3 genomes AF: 0.818 AC: 124336 AN: 152064 Hom.: 51442 Cov.: 32

Gnomad AFR AF: 0.710

Gnomad AMI AF: 0.853

Gnomad AMR AF: 0.839

Gnomad ASJ AF: 0.795

Gnomad EAS AF: 0.613

Gnomad SAS AF: 0.903

Gnomad FIN AF: 0.830

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.886

Gnomad OTH AF: 0.826

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

GnomAD4 genome AF: 0.817 AC: 124393 AN: 152182 Hom.: 51456 Cov.: 32 AF XY: 0.815 AC XY: 60645 AN XY: 74372

Gnomad4 AFR AF: 0.709

Gnomad4 AMR AF: 0.840

Gnomad4 ASJ AF: 0.795

Gnomad4 EAS AF: 0.611

Gnomad4 SAS AF: 0.903

Gnomad4 FIN AF: 0.830

Gnomad4 NFE AF: 0.886

Gnomad4 OTH AF: 0.828

Alfa AF: 0.831 Hom.: 11056

Bravo AF: 0.811

Asia WGS AF: 0.786 AC: 2732 AN: 3476

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	-0.92
CADD	Benign	6.8
DANN	Benign	0.74

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: rs360722; hg19: chr11-112026703;