Genetic Variant NM_001393487.1:c.70+66C>G (chr2-102423413-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001393487.1(IL18RAP):c.70+66C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 1,259,924 control chromosomes in the GnomAD database, including 22,366 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 0.22 ( 4086 hom., cov: 33)

Exomes 𝑓: 0.17 ( 18280 hom. )

Consequence

IL18RAP
NM_001393487.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.482

Publications

17 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=-0.84).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL18RAP	NM_001393487.1 link	c.70+66C>G		intron_variant	Intron 1 of 9	ENST00000687160.1	NP_001380416.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL18RAP	ENST00000687160.1 link	c.70+66C>G		intron_variant	Intron 1 of 9		NM_001393487.1	ENSP00000510345.1		O95256-1

Frequencies

GnomAD3 genomes

AF:

0.218

AC:

33058

AN:

151982

Hom.:

4084

Cov.:

show subpopulations

Gnomad AFR

AF:

0.328

Gnomad AMI

AF:

0.183

Gnomad AMR

AF:

0.171

Gnomad ASJ

AF:

0.252

Gnomad EAS

AF:

0.0952

Gnomad SAS

AF:

0.0770

Gnomad FIN

AF:

0.191

Gnomad MID

AF:

0.199

Gnomad NFE

AF:

0.183

Gnomad OTH

AF:

0.213

GnomAD4 exome

AF:

0.174

AC:

192674

AN:

1107824

Hom.:

18280

AF XY:

0.171

AC XY:

96924

AN XY:

567846

show subpopulations

African (AFR)

AF:

0.343

AC:

9048

AN:

26390

American (AMR)

AF:

0.115

AC:

5075

AN:

44166

Ashkenazi Jewish (ASJ)

AF:

0.260

AC:

6177

AN:

23776

East Asian (EAS)

AF:

0.124

AC:

4710

AN:

38030

South Asian (SAS)

AF:

0.0676

AC:

5344

AN:

79090

European-Finnish (FIN)

AF:

0.186

AC:

9868

AN:

53176

Middle Eastern (MID)

AF:

0.230

AC:

1163

AN:

5050

European-Non Finnish (NFE)

AF:

0.180

AC:

142377

AN:

789356

Other (OTH)

AF:

0.183

AC:

8912

AN:

48790

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

8268

16535

24803

33070

41338

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4182

8364

12546

16728

20910

<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:

0.218

AC:

33088

AN:

152100

Hom.:

4086

Cov.:

AF XY:

0.214

AC XY:

15913

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.328

AC:

13608

AN:

41458

American (AMR)

AF:

0.171

AC:

2611

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.252

AC:

874

AN:

3472

East Asian (EAS)

AF:

0.0954

AC:

494

AN:

5176

South Asian (SAS)

AF:

0.0764

AC:

369

AN:

4830

European-Finnish (FIN)

AF:

0.191

AC:

2023

AN:

10574

Middle Eastern (MID)

AF:

0.211

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.183

AC:

12430

AN:

67992

Other (OTH)

AF:

0.213

AC:

450

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1294

2589

3883

5178

6472

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

324

648

972

1296

1620

<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:

0.202

Hom.:

428

Bravo

AF:

0.219

Asia WGS

AF:

0.0940

AC:

327

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.0

(source)

DANN

Benign

0.39

PhyloP100

-0.48

PromoterAI

0.018

Neutral

(source)

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over