dbSNP rs1420105: IL18RAP:c.-619T>C (chr2-102418659-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.-619T>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 152,116 control chromosomes in the GnomAD database, including 23,638 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 0.54 ( 23630 hom., cov: 32)

Exomes 𝑓: 0.48 ( 8 hom. )

Consequence

IL18RAP
NM_003853.4 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.54

Publications

15 publications found

Variant links:

COSMIC-nc: COSV51824622

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=-0.79).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
IL18RAP	NM_003853.4 link	c.-619T>C	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 12	NP_003844.1
IL18RAP	NM_001393488.1 link	c.-1249T>C	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 12	NP_001380417.1
IL18RAP	NM_003853.4 link	c.-619T>C	5_prime_UTR_variant	Exon 1 of 12	NP_003844.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL18RAP	ENST00000264260.6 link	c.-619T>C		upstream_gene_variant		1		ENSP00000264260.2

Frequencies

GnomAD3 genomes

AF:

0.535

AC:

81283

AN:

151916

Hom.:

23599

Cov.:

show subpopulations

Gnomad AFR

AF:

0.733

Gnomad AMI

AF:

0.468

Gnomad AMR

AF:

0.415

Gnomad ASJ

AF:

0.614

Gnomad EAS

AF:

0.150

Gnomad SAS

AF:

0.269

Gnomad FIN

AF:

0.542

Gnomad MID

AF:

0.535

Gnomad NFE

AF:

0.486

Gnomad OTH

AF:

0.526

GnomAD4 exome

AF:

0.476

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.476

AC:

AN:

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: 0.533

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:

0.535

AC:

81366

AN:

152032

Hom.:

23630

Cov.:

AF XY:

0.529

AC XY:

39290

AN XY:

74278

show subpopulations

African (AFR)

AF:

0.733

AC:

30393

AN:

41466

American (AMR)

AF:

0.414

AC:

6324

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.614

AC:

2133

AN:

3472

East Asian (EAS)

AF:

0.150

AC:

778

AN:

5184

South Asian (SAS)

AF:

0.269

AC:

1296

AN:

4824

European-Finnish (FIN)

AF:

0.542

AC:

5720

AN:

10560

Middle Eastern (MID)

AF:

0.545

AC:

159

AN:

292

European-Non Finnish (NFE)

AF:

0.486

AC:

33033

AN:

67934

Other (OTH)

AF:

0.522

AC:

1103

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1797

3594

5391

7188

8985

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

674

1348

2022

2696

3370

<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:

0.512

Hom.:

4148

Bravo

AF:

0.536

Asia WGS

AF:

0.234

AC:

813

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

(source)

DANN

Benign

0.76

PhyloP100

1.5

PromoterAI

-0.084

Neutral

(source)

Splicing

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