dbSNP rs1420106: IL18RAP:c.-694A>G (chr2-102418584-A-G) – 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.-694A>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.774 in 152,102 control chromosomes in the GnomAD database, including 46,600 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 ( 46599 hom., cov: 32)

Exomes 𝑓: 0.75 ( 1 hom. )

Consequence

IL18RAP
ENST00000264260.6 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0490

Publications

44 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=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.887 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Protein	UniProt
IL18RAP	NM_001393486.1 link	c.-554A>G	upstream_gene_variant	NP_001380415.1
IL18RAP	NM_003853.4 link	c.-694A>G	upstream_gene_variant	NP_003844.1	O95256-1
IL18RAP	NM_001393488.1 link	c.-1324A>G	upstream_gene_variant	NP_001380417.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL18RAP	ENST00000264260.6 link	c.-694A>G		upstream_gene_variant		1		ENSP00000264260.2		O95256-1

Frequencies

GnomAD3 genomes

AF:

0.774

AC:

117664

AN:

151980

Hom.:

46551

Cov.:

show subpopulations

Gnomad AFR

AF:

0.894

Gnomad AMI

AF:

0.676

Gnomad AMR

AF:

0.605

Gnomad ASJ

AF:

0.767

Gnomad EAS

AF:

0.551

Gnomad SAS

AF:

0.549

Gnomad FIN

AF:

0.812

Gnomad MID

AF:

0.756

Gnomad NFE

AF:

0.768

Gnomad OTH

AF:

0.759

GnomAD4 exome

AF:

0.750

AC:

AN:

Hom.:

AF XY:

0.750

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.774

AC:

117763

AN:

152098

Hom.:

46599

Cov.:

AF XY:

0.768

AC XY:

57087

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.894

AC:

37131

AN:

41516

American (AMR)

AF:

0.604

AC:

9214

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.767

AC:

2663

AN:

3472

East Asian (EAS)

AF:

0.552

AC:

2848

AN:

5160

South Asian (SAS)

AF:

0.549

AC:

2646

AN:

4820

European-Finnish (FIN)

AF:

0.812

AC:

8584

AN:

10576

Middle Eastern (MID)

AF:

0.752

AC:

221

AN:

294

European-Non Finnish (NFE)

AF:

0.768

AC:

52233

AN:

67972

Other (OTH)

AF:

0.761

AC:

1608

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1312

2624

3936

5248

6560

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:

0.757

Hom.:

52068

Bravo

AF:

0.764

Asia WGS

AF:

0.583

AC:

2030

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

(source)

DANN

Benign

0.58

PhyloP100

-0.049

PromoterAI

0.080

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