Genetic Variant ENST00000264260.6:c.-337-132C>T (chr2-102419429-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 ENST00000264260.6(IL18RAP):c.-337-132C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 152,174 control chromosomes in the GnomAD database, including 2,469 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 0.16 ( 2467 hom., cov: 32)

Exomes 𝑓: 0.16 ( 2 hom. )

Consequence

IL18RAP
ENST00000264260.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0810

Publications

12 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=-0.81).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
IL18RAP	NM_001393486.1 link	c.-337-132C>T	intron_variant	Intron 2 of 12	NP_001380415.1
IL18RAP	NM_003853.4 link	c.-337-132C>T	intron_variant	Intron 1 of 11	NP_003844.1	O95256-1
IL18RAP	NM_001393488.1 link	c.-967-132C>T	intron_variant	Intron 1 of 11	NP_001380417.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL18RAP	ENST00000264260.6 link	c.-337-132C>T		intron_variant	Intron 1 of 11	1		ENSP00000264260.2		O95256-1
IL18RAP	ENST00000450855.1 link	c.-469C>T		upstream_gene_variant		4		ENSP00000389815.1		C9JLE2

Frequencies

GnomAD3 genomes

AF:

0.165

AC:

25080

AN:

151932

Hom.:

2466

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0670

Gnomad AMI

AF:

0.171

Gnomad AMR

AF:

0.144

Gnomad ASJ

AF:

0.129

Gnomad EAS

AF:

0.229

Gnomad SAS

AF:

0.227

Gnomad FIN

AF:

0.207

Gnomad MID

AF:

0.187

Gnomad NFE

AF:

0.215

Gnomad OTH

AF:

0.170

GnomAD4 exome

AF:

0.156

AC:

AN:

122

Hom.:

Cov.:

AF XY:

0.153

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.161

AC:

AN:

112

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.100

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.522

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.165

AC:

25085

AN:

152052

Hom.:

2467

Cov.:

AF XY:

0.166

AC XY:

12301

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.0668

AC:

2770

AN:

41492

American (AMR)

AF:

0.144

AC:

2195

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.129

AC:

449

AN:

3468

East Asian (EAS)

AF:

0.230

AC:

1184

AN:

5158

South Asian (SAS)

AF:

0.227

AC:

1092

AN:

4816

European-Finnish (FIN)

AF:

0.207

AC:

2186

AN:

10572

Middle Eastern (MID)

AF:

0.173

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.215

AC:

14626

AN:

67944

Other (OTH)

AF:

0.178

AC:

376

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1028

2056

3084

4112

5140

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

296

592

888

1184

1480

<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:

0.193

Hom.:

740

Bravo

AF:

0.155

Asia WGS

AF:

0.245

AC:

853

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.1

(source)

DANN

Benign

0.77

PhyloP100

0.081

PromoterAI

-0.012

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