11-112150193-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_001562.4(IL18):c.105A>C(p.Ser35=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 1,552,018 control chromosomes in the GnomAD database, including 66,212 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.27 (5863 hom., cov: 32)
  • Exomes 𝑓: 0.29 (60349 hom.)
• Consequence: IL18 NM_001562.4 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.0950

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 11-112150193-T-G is Benign according to our data. Variant chr11-112150193-T-G is described in ClinVar as [Benign]. Clinvar id is 812621.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-112150193-T-G is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.095 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL18	NM_001562.4	c.105A>C	p.Ser35=	synonymous_variant	4/6	ENST00000280357.12
IL18	NM_001386420.1	c.105A>C	p.Ser35=	synonymous_variant	4/6
IL18	NM_001243211.2	c.93A>C	p.Ser31=	synonymous_variant	3/5
IL18	XM_011542805.2	c.93A>C	p.Ser31=	synonymous_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL18	ENST00000280357.12	c.105A>C	p.Ser35=	synonymous_variant	4/6	1	NM_001562.4	P3

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41208 AN: 152004 Hom.: 5865 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.270

GnomAD3 exomes AF: 0.285 AC: 68341 AN: 239770 Hom.: 10054 AF XY: 0.285 AC XY: 37053 AN XY: 130020

Gnomad AFR exome AF: 0.197

Gnomad AMR exome AF: 0.332

Gnomad ASJ exome AF: 0.291

Gnomad EAS exome AF: 0.139

Gnomad SAS exome AF: 0.245

Gnomad FIN exome AF: 0.308

Gnomad NFE exome AF: 0.312

Gnomad OTH exome AF: 0.293

GnomAD4 exome AF: 0.290 AC: 406317 AN: 1399896 Hom.: 60349 Cov.: 26 AF XY: 0.290 AC XY: 202736 AN XY: 699340

Gnomad4 AFR exome AF: 0.187

Gnomad4 AMR exome AF: 0.331

Gnomad4 ASJ exome AF: 0.285

Gnomad4 EAS exome AF: 0.128

Gnomad4 SAS exome AF: 0.244

Gnomad4 FIN exome AF: 0.310

Gnomad4 NFE exome AF: 0.301

Gnomad4 OTH exome AF: 0.281

GnomAD4 genome AF: 0.271 AC: 41192 AN: 152122 Hom.: 5863 Cov.: 32 AF XY: 0.271 AC XY: 20120 AN XY: 74362

Gnomad4 AFR AF: 0.201

Gnomad4 AMR AF: 0.321

Gnomad4 ASJ AF: 0.292

Gnomad4 EAS AF: 0.128

Gnomad4 SAS AF: 0.230

Gnomad4 FIN AF: 0.311

Gnomad4 NFE AF: 0.309

Gnomad4 OTH AF: 0.266

Alfa AF: 0.296 Hom.: 8940

Bravo AF: 0.270

Asia WGS AF: 0.193 AC: 673 AN: 3474

EpiCase AF: 0.297

EpiControl AF: 0.300

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	-0.47
Cadd	Benign	4.3
Dann	Benign	0.88

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: rs549908; hg19: chr11-112020916; COSMIC: COSV54780703; COSMIC: COSV54780703;