dbSNP rs2272128: IL18RAP:c.70+122G>A (chr2-102423469-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_001393487.1(IL18RAP):c.70+122G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 896,870 control chromosomes in the GnomAD database, including 248,947 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 0.77 ( 46418 hom., cov: 32)

Exomes 𝑓: 0.73 ( 202529 hom. )

Consequence

IL18RAP
NM_001393487.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.68

Publications

25 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:

Genome browser will be placed here

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=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL18RAP	NM_001393487.1 link	c.70+122G>A		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+122G>A		intron_variant	Intron 1 of 9		NM_001393487.1	ENSP00000510345.1

Frequencies

GnomAD3 genomes

AF:

0.773

AC:

117490

AN:

152044

Hom.:

46371

Cov.:

show subpopulations

Gnomad AFR

AF:

0.889

Gnomad AMI

AF:

0.674

Gnomad AMR

AF:

0.604

Gnomad ASJ

AF:

0.767

Gnomad EAS

AF:

0.552

Gnomad SAS

AF:

0.551

Gnomad FIN

AF:

0.812

Gnomad MID

AF:

0.756

Gnomad NFE

AF:

0.768

Gnomad OTH

AF:

0.756

GnomAD4 exome

AF:

0.729

AC:

543144

AN:

744706

Hom.:

202529

AF XY:

0.722

AC XY:

283883

AN XY:

393030

show subpopulations

African (AFR)

AF:

0.893

AC:

17142

AN:

19202

American (AMR)

AF:

0.463

AC:

17878

AN:

38616

Ashkenazi Jewish (ASJ)

AF:

0.768

AC:

14306

AN:

18626

East Asian (EAS)

AF:

0.553

AC:

19997

AN:

36176

South Asian (SAS)

AF:

0.549

AC:

35712

AN:

65016

European-Finnish (FIN)

AF:

0.812

AC:

40908

AN:

50398

Middle Eastern (MID)

AF:

0.773

AC:

3196

AN:

4132

European-Non Finnish (NFE)

AF:

0.771

AC:

367129

AN:

476338

Other (OTH)

AF:

0.742

AC:

26876

AN:

36202

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

7073

14146

21219

28292

35365

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4904

9808

14712

19616

24520

<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:

0.773

AC:

117588

AN:

152164

Hom.:

46418

Cov.:

AF XY:

0.767

AC XY:

57005

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.889

AC:

36947

AN:

41542

American (AMR)

AF:

0.603

AC:

9207

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.767

AC:

2661

AN:

3470

East Asian (EAS)

AF:

0.553

AC:

2848

AN:

5154

South Asian (SAS)

AF:

0.551

AC:

2658

AN:

4820

European-Finnish (FIN)

AF:

0.812

AC:

8594

AN:

10590

Middle Eastern (MID)

AF:

0.752

AC:

221

AN:

294

European-Non Finnish (NFE)

AF:

0.768

AC:

52239

AN:

68000

Other (OTH)

AF:

0.759

AC:

1600

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1286

2572

3859

5145

6431

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

854

1708

2562

3416

4270

<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:

0.747

Hom.:

26314

Bravo

AF:

0.762

Asia WGS

AF:

0.582

AC:

2024

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.020

(source)

DANN

Benign

0.38

PhyloP100

-1.7

PromoterAI

-0.0026

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