rs11465716

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001393487.1(IL18RAP):c.1048G>A(p.Val350Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00079 in 1,614,122 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0037 ( 8 hom., cov: 33)

Exomes 𝑓: 0.00048 ( 3 hom. )

Consequence

IL18RAP
NM_001393487.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.179

Publications

10 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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0044792593).

BP6

Variant 2-102445316-G-A is Benign according to our data. Variant chr2-102445316-G-A is described in ClinVar as Benign. ClinVar VariationId is 708523.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

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	HGVSp	Effect	Exon Rank	Protein	UniProt
IL18RAP	NM_001393487.1	MANE Select	c.1048G>A	p.Val350Ile	missense	Exon 7 of 10	NP_001380416.1	O95256-1
IL18RAP	NM_001393486.1		c.1048G>A	p.Val350Ile	missense	Exon 10 of 13	NP_001380415.1	O95256-1
IL18RAP	NM_003853.4		c.1048G>A	p.Val350Ile	missense	Exon 9 of 12	NP_003844.1	O95256-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IL18RAP	ENST00000687160.1	MANE Select	c.1048G>A	p.Val350Ile	missense	Exon 7 of 10	ENSP00000510345.1	O95256-1
IL18RAP	ENST00000264260.6	TSL:1	c.1048G>A	p.Val350Ile	missense	Exon 9 of 12	ENSP00000264260.2	O95256-1
IL18RAP	ENST00000409369.1	TSL:1	c.622G>A	p.Val208Ile	missense	Exon 7 of 10	ENSP00000387201.1	O95256-2

Frequencies

GnomAD3 genomes

AF:

0.00375

AC:

571

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0126

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00150

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00143

GnomAD2 exomes

AF:

0.00112

AC:

282

AN:

251330

AF XY:

0.000795

show subpopulations

Gnomad AFR exome

AF:

0.0130

Gnomad AMR exome

AF:

0.00113

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000218

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.000176

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000482

AC:

704

AN:

1461822

Hom.:

Cov.:

AF XY:

0.000375

AC XY:

273

AN XY:

727206

show subpopulations

African (AFR)

AF:

0.0140

AC:

470

AN:

33476

American (AMR)

AF:

0.00123

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26134

East Asian (EAS)

AF:

0.000151

AC:

AN:

39694

South Asian (SAS)

AF:

0.00

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.000187

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.000520

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000971

AC:

108

AN:

1111964

Other (OTH)

AF:

0.000844

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

104

139

174

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.00375

AC:

571

AN:

152300

Hom.:

Cov.:

AF XY:

0.00375

AC XY:

279

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.0126

AC:

524

AN:

41562

American (AMR)

AF:

0.00150

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.000377

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000206

AC:

AN:

68018

Other (OTH)

AF:

0.00142

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

118

148

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.00155

Hom.:

Bravo

AF:

0.00452

ESP6500AA

AF:

0.0152

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00131

AC:

159

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000296

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.056

(source)

DANN

Benign

0.69

DEOGEN2

Benign

0.090

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0047

LIST_S2

Benign

0.58

MetaRNN

Benign

0.0045

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.8

PhyloP100

-0.18

PrimateAI

Benign

0.25

PROVEAN

Benign

0.14

REVEL

Benign

0.027

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0060

Vest4

0.045

MVP

0.055

MPC

0.14

ClinPred

0.0073

GERP RS

-5.0

Varity_R

0.044

gMVP

0.59

Mutation Taster

=99/1

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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