Genetic Variant NM_001393487.1:c.1385-70C>T (chr2-102451696-C-T) – 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.1385-70C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0751 in 1,261,280 control chromosomes in the GnomAD database, including 4,135 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 0.069 ( 477 hom., cov: 33)

Exomes 𝑓: 0.076 ( 3658 hom. )

Consequence

IL18RAP
NM_001393487.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0770

Publications

13 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 (NFE) allele frequency at 95% confidence interval = 0.0867 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393487.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
IL18RAP	NM_001393487.1	MANE Select	c.1385-70C>T	intron	N/A	NP_001380416.1
IL18RAP	NM_001393486.1		c.1385-70C>T	intron	N/A	NP_001380415.1
IL18RAP	NM_003853.4		c.1385-70C>T	intron	N/A	NP_003844.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
IL18RAP	ENST00000687160.1	MANE Select	c.1385-70C>T	intron	N/A	ENSP00000510345.1
IL18RAP	ENST00000264260.6	TSL:1	c.1385-70C>T	intron	N/A	ENSP00000264260.2
IL18RAP	ENST00000409369.1	TSL:1	c.959-70C>T	intron	N/A	ENSP00000387201.1

Frequencies

GnomAD3 genomes

AF:

0.0694

AC:

10558

AN:

152088

Hom.:

477

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0396

Gnomad AMI

AF:

0.0888

Gnomad AMR

AF:

0.0588

Gnomad ASJ

AF:

0.0476

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0157

Gnomad FIN

AF:

0.144

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0886

Gnomad OTH

AF:

0.0680

GnomAD4 exome

AF:

0.0758

AC:

84107

AN:

1109072

Hom.:

3658

AF XY:

0.0743

AC XY:

41466

AN XY:

558206

show subpopulations

African (AFR)

AF:

0.0363

AC:

928

AN:

25598

American (AMR)

AF:

0.0462

AC:

1584

AN:

34280

Ashkenazi Jewish (ASJ)

AF:

0.0377

AC:

734

AN:

19480

East Asian (EAS)

AF:

0.000423

AC:

AN:

37808

South Asian (SAS)

AF:

0.0159

AC:

1063

AN:

66956

European-Finnish (FIN)

AF:

0.130

AC:

6395

AN:

49050

Middle Eastern (MID)

AF:

0.0384

AC:

187

AN:

4870

European-Non Finnish (NFE)

AF:

0.0850

AC:

69946

AN:

823062

Other (OTH)

AF:

0.0678

AC:

3254

AN:

47968

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

3952

7904

11857

15809

19761

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2218

4436

6654

8872

11090

<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:

0.0694

AC:

10556

AN:

152208

Hom.:

477

Cov.:

AF XY:

0.0702

AC XY:

5228

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.0395

AC:

1640

AN:

41526

American (AMR)

AF:

0.0587

AC:

898

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0476

AC:

165

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5180

South Asian (SAS)

AF:

0.0157

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.144

AC:

1523

AN:

10594

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0885

AC:

6021

AN:

68008

Other (OTH)

AF:

0.0673

AC:

142

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

501

1002

1504

2005

2506

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

240

360

480

600

<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:

0.0758

Hom.:

390

Bravo

AF:

0.0618

Asia WGS

AF:

0.00895

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

8.0

(source)

DANN

Benign

0.53

PhyloP100

-0.077

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over