Variant chr11-112150193-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

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 (★).

Frequency

Genomes: 𝑓 0.27 ( 5863 hom., cov: 32)

Exomes 𝑓: 0.29 ( 60349 hom. )

Consequence

IL18
NM_001562.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.0950

Variant links:

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]

IL18 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 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 criteria_provided_single_submitter, 1 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	Protein
IL18	NM_001562.4 linkuse as main transcript	c.105A>C	p.Ser35=	synonymous_variant	4/6	ENST00000280357.12	NP_001553.1
IL18	NM_001386420.1 linkuse as main transcript	c.105A>C	p.Ser35=	synonymous_variant	4/6		NP_001373349.1
IL18	NM_001243211.2 linkuse as main transcript	c.93A>C	p.Ser31=	synonymous_variant	3/5		NP_001230140.1
IL18	XM_011542805.2 linkuse as main transcript	c.93A>C	p.Ser31=	synonymous_variant	3/5		XP_011541107.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL18	ENST00000280357.12 linkuse as main transcript	c.105A>C	p.Ser35=	synonymous_variant	4/6	1	NM_001562.4	ENSP00000280357	P3	Q14116-1

Frequencies

GnomAD3 genomes

AF:

0.271

AC:

41208

AN:

152004

Hom.:

5865

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.290

AC XY:

202736

AN XY:

699340

show subpopulations

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.:

AF XY:

0.271

AC XY:

20120

AN XY:

74362

show subpopulations

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:2

Revision: criteria provided, single submitter

LINK: link

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

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over