dbSNP rs5744280: IL18:c.361-1974C>T (chr11-112145791-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001562.4(IL18):c.361-1974C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 151,896 control chromosomes in the GnomAD database, including 9,427 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.35 ( 9427 hom., cov: 32)

Consequence

IL18
NM_001562.4 intron

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.505

Publications

22 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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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 11-112145791-G-A is Benign according to our data. Variant chr11-112145791-G-A is described in ClinVar as Benign. ClinVar VariationId is 812622.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.551 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.361-1974C>T	intron	N/A	NP_001553.1	Q14116-1
IL18	NM_001386420.1		c.361-1974C>T	intron	N/A	NP_001373349.1	Q14116-1
IL18	NM_001243211.2		c.349-1974C>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.361-1974C>T	intron	N/A	ENSP00000280357.7	Q14116-1
IL18	ENST00000524595.6	TSL:1	c.349-1974C>T	intron	N/A	ENSP00000434561.1	Q14116-2
IL18	ENST00000525547.5	TSL:1	n.1137-1974C>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.349

AC:

52976

AN:

151778

Hom.:

9407

Cov.:

show subpopulations

Gnomad AFR

AF:

0.355

Gnomad AMI

AF:

0.281

Gnomad AMR

AF:

0.360

Gnomad ASJ

AF:

0.364

Gnomad EAS

AF:

0.445

Gnomad SAS

AF:

0.568

Gnomad FIN

AF:

0.282

Gnomad MID

AF:

0.411

Gnomad NFE

AF:

0.330

Gnomad OTH

AF:

0.371

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

GnomAD4 genome

AF:

0.349

AC:

53027

AN:

151896

Hom.:

9427

Cov.:

AF XY:

0.352

AC XY:

26156

AN XY:

74220

show subpopulations

African (AFR)

AF:

0.354

AC:

14660

AN:

41370

American (AMR)

AF:

0.361

AC:

5510

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.364

AC:

1264

AN:

3472

East Asian (EAS)

AF:

0.445

AC:

2299

AN:

5166

South Asian (SAS)

AF:

0.569

AC:

2745

AN:

4824

European-Finnish (FIN)

AF:

0.282

AC:

2972

AN:

10524

Middle Eastern (MID)

AF:

0.398

AC:

117

AN:

294

European-Non Finnish (NFE)

AF:

0.330

AC:

22410

AN:

67956

Other (OTH)

AF:

0.377

AC:

795

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1756

3513

5269

7026

8782

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

528

1056

1584

2112

2640

<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:

0.339

Hom.:

6281

Bravo

AF:

0.350

Asia WGS

AF:

0.507

AC:

1764

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Three Vessel Coronary Disease (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

4.5

(source)

DANN

Benign

0.72

PhyloP100

0.51

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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