Variant 11-112153608-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001562.4(IL18):c.80-5C>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000396 in 1,551,314 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0022 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00020 ( 1 hom. )

Consequence

IL18
NM_001562.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0008804

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.892

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 11-112153608-G-T is Benign according to our data. Variant chr11-112153608-G-T is described in ClinVar as [Benign]. Clinvar id is 786213.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
IL18	NM_001562.4 linkuse as main transcript	c.80-5C>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	ENST00000280357.12	NP_001553.1
IL18	NM_001243211.2 linkuse as main transcript	c.79+1367C>A	intron_variant		NP_001230140.1
IL18	NM_001386420.1 linkuse as main transcript	c.80-5C>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		NP_001373349.1
IL18	XM_011542805.2 linkuse as main transcript	c.79+1367C>A	intron_variant		XP_011541107.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL18	ENST00000280357.12 linkuse as main transcript	c.80-5C>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001562.4	ENSP00000280357	P3	Q14116-1

Frequencies

GnomAD3 genomes

AF:

0.00220

AC:

335

AN:

152058

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00758

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000852

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000559

AC:

127

AN:

227120

Hom.:

AF XY:

0.000387

AC XY:

AN XY:

124072

show subpopulations

Gnomad AFR exome

AF:

0.00779

Gnomad AMR exome

AF:

0.000395

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000189

Gnomad OTH exome

AF:

0.000188

GnomAD4 exome

AF:

0.000199

AC:

279

AN:

1399138

Hom.:

Cov.:

AF XY:

0.000182

AC XY:

127

AN XY:

698152

show subpopulations

Gnomad4 AFR exome

AF:

0.00739

Gnomad4 AMR exome

AF:

0.000471

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000560

Gnomad4 OTH exome

AF:

0.000382

GnomAD4 genome

AF:

0.00221

AC:

336

AN:

152176

Hom.:

Cov.:

AF XY:

0.00218

AC XY:

162

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.00759

Gnomad4 AMR

AF:

0.000851

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00133

Hom.:

Bravo

AF:

0.00227

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

1.5

DANN

Benign

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00088

dbscSNV1_RF

Benign

0.034

SpliceAI score (max)

0.060

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