dbSNP rs7106524: IL18:c.-9+993C>T (chr11-112162913-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001562.4(IL18):c.-9+993C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 152,042 control chromosomes in the GnomAD database, including 10,619 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.37 ( 10619 hom., cov: 32)

Consequence

IL18
NM_001562.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.23

Publications

15 publications found

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:

ENSG00000255292 (HGNC:):

ENSG00000255292 links:

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new If you want to explore the variant's impact on the transcript NM_001562.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.57 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001562.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IL18	NM_001562.4	MANE Select	c.-9+993C>T	intron	N/A	NP_001553.1	Q14116-1
IL18	NM_001386420.1		c.-30+993C>T	intron	N/A	NP_001373349.1	Q14116-1
IL18	NM_001243211.2		c.-9+993C>T	intron	N/A	NP_001230140.1	Q14116-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IL18	ENST00000280357.12	TSL:1 MANE Select	c.-9+993C>T	intron	N/A	ENSP00000280357.7	Q14116-1
IL18	ENST00000524595.6	TSL:1	c.-9+993C>T	intron	N/A	ENSP00000434561.1	Q14116-2
ENSG00000255292	ENST00000532699.1	TSL:3	n.315-7506G>A	intron	N/A	ENSP00000456434.1	H3BRW5

Frequencies

GnomAD3 genomes

AF:

0.371

AC:

56339

AN:

151924

Hom.:

10601

Cov.:

show subpopulations

Gnomad AFR

AF:

0.371

Gnomad AMI

AF:

0.278

Gnomad AMR

AF:

0.379

Gnomad ASJ

AF:

0.386

Gnomad EAS

AF:

0.456

Gnomad SAS

AF:

0.588

Gnomad FIN

AF:

0.290

Gnomad MID

AF:

0.418

Gnomad NFE

AF:

0.360

Gnomad OTH

AF:

0.386

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

GnomAD4 genome

AF:

0.371

AC:

56390

AN:

152042

Hom.:

10619

Cov.:

AF XY:

0.373

AC XY:

27723

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.370

AC:

15350

AN:

41448

American (AMR)

AF:

0.379

AC:

5788

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.386

AC:

1340

AN:

3470

East Asian (EAS)

AF:

0.456

AC:

2357

AN:

5168

South Asian (SAS)

AF:

0.588

AC:

2835

AN:

4818

European-Finnish (FIN)

AF:

0.290

AC:

3067

AN:

10566

Middle Eastern (MID)

AF:

0.405

AC:

119

AN:

294

European-Non Finnish (NFE)

AF:

0.360

AC:

24450

AN:

67982

Other (OTH)

AF:

0.393

AC:

831

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1840

3681

5521

7362

9202

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

554

1108

1662

2216

2770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.361

Hom.:

1712

Bravo

AF:

0.372

Asia WGS

AF:

0.523

AC:

1818

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

1.7

(source)

DANN

Benign

0.67

PhyloP100

-1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over