Genetic Variant IL18RAP:c.-363T>C (chr2-102418915-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_003853.4(IL18RAP):c.-363T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0784 in 152,378 control chromosomes in the GnomAD database, including 563 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 0.078 ( 563 hom., cov: 33)

Exomes 𝑓: 0.11 ( 0 hom. )

Consequence

IL18RAP
NM_003853.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0440

Publications

9 publications found

Variant links:

Genes affected

IL18RAP (HGNC:5989): (interleukin 18 receptor accessory protein) The protein encoded by this gene is an accessory subunit of the heterodimeric receptor for interleukin 18 (IL18), a proinflammatory cytokine involved in inducing cell-mediated immunity. This protein enhances the IL18-binding activity of the IL18 receptor and plays a role in signaling by IL18. Mutations in this gene are associated with Crohn's disease and inflammatory bowel disease, and susceptibility to celiac disease and leprosy. Alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known. [provided by RefSeq, Feb 2014]

IL18RAP links:

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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=-0.68).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0847 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003853.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
IL18RAP	NM_001393486.1	c.-363T>C	5_prime_UTR	Exon 2 of 13	NP_001380415.1	O95256-1
IL18RAP	NM_003853.4	c.-363T>C	5_prime_UTR	Exon 1 of 12	NP_003844.1	O95256-1
IL18RAP	NM_001393488.1	c.-993T>C	5_prime_UTR	Exon 1 of 12	NP_001380417.1	O95256-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL18RAP	ENST00000264260.6	TSL:1	c.-363T>C		5_prime_UTR	Exon 1 of 12	ENSP00000264260.2	O95256-1
	IL18RAP	ENST00000863555.1		c.-363T>C		5_prime_UTR	Exon 2 of 13	ENSP00000533614.1

Frequencies

GnomAD3 genomes

AF:

0.0784

AC:

11925

AN:

152122

Hom.:

562

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0534

Gnomad AMI

AF:

0.0440

Gnomad AMR

AF:

0.0725

Gnomad ASJ

AF:

0.187

Gnomad EAS

AF:

0.0404

Gnomad SAS

AF:

0.0844

Gnomad FIN

AF:

0.106

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.0866

Gnomad OTH

AF:

0.102

GnomAD4 exome

AF:

0.109

AC:

AN:

138

Hom.:

Cov.:

AF XY:

0.132

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.109

AC:

AN:

138

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0784

AC:

11929

AN:

152240

Hom.:

563

Cov.:

AF XY:

0.0787

AC XY:

5860

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.0534

AC:

2218

AN:

41564

American (AMR)

AF:

0.0723

AC:

1107

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.187

AC:

648

AN:

3470

East Asian (EAS)

AF:

0.0403

AC:

209

AN:

5186

South Asian (SAS)

AF:

0.0853

AC:

412

AN:

4828

European-Finnish (FIN)

AF:

0.106

AC:

1125

AN:

10582

Middle Eastern (MID)

AF:

0.228

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0866

AC:

5888

AN:

67992

Other (OTH)

AF:

0.102

AC:

215

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

563

1126

1690

2253

2816

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

272

408

544

680

<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:

0.0794

Hom.:

193

Bravo

AF:

0.0745

Asia WGS

AF:

0.0740

AC:

254

AN:

3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Benign

0.82

PhyloP100

0.044

PromoterAI

0.016

Neutral

(source)

Mutation Taster

=299/1

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over