rs5743673

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 1P and 16B. PP3BP6_Very_StrongBA1

The NM_001039660.2(IL18BP):c.362G>A(p.Arg121Gln) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00432 in 1,614,050 control chromosomes in the GnomAD database, including 251 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R121W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.023 ( 132 hom., cov: 32)

Exomes 𝑓: 0.0024 ( 119 hom. )

Consequence

IL18BP
NM_001039660.2 missense, splice_region

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.86

Publications

13 publications found

Variant links:

Genes affected

IL18BP (HGNC:5987): (interleukin 18 binding protein) The protein encoded by this gene functions as an inhibitor of the proinflammatory cytokine, IL18. It binds IL18, prevents the binding of IL18 to its receptor, and thus inhibits IL18-induced IFN-gamma production, resulting in reduced T-helper type 1 immune responses. This protein is constitutively expressed and secreted in mononuclear cells. Elevated level of this protein is detected in the intestinal tissues of patients with Crohn's disease. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Feb 2011]

IL18BP Gene-Disease associations (from GenCC):

hepatitis, fulminant viral, susceptibility to
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

IL18BP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

BP6

Variant 11-72001407-G-A is Benign according to our data. Variant chr11-72001407-G-A is described in ClinVar as Benign. ClinVar VariationId is 787089.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0774 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL18BP	NM_001039660.2 link	c.362G>A	p.Arg121Gln	missense_variant, splice_region_variant	Exon 5 of 6	ENST00000393703.9	NP_001034749.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL18BP	ENST00000393703.9 link	c.362G>A	p.Arg121Gln	missense_variant, splice_region_variant	Exon 5 of 6	3	NM_001039660.2	ENSP00000377306.4

Frequencies

GnomAD3 genomes

AF:

0.0229

AC:

3481

AN:

152188

Hom.:

132

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0798

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00785

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.0143

GnomAD2 exomes

AF:

0.00575

AC:

1433

AN:

249156

AF XY:

0.00441

show subpopulations

Gnomad AFR exome

AF:

0.0820

Gnomad AMR exome

AF:

0.00359

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000177

Gnomad OTH exome

AF:

0.00264

GnomAD4 exome

AF:

0.00239

AC:

3491

AN:

1461742

Hom.:

119

Cov.:

AF XY:

0.00210

AC XY:

1526

AN XY:

727150

show subpopulations

African (AFR)

AF:

0.0867

AC:

2902

AN:

33480

American (AMR)

AF:

0.00385

AC:

172

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39694

South Asian (SAS)

AF:

0.000209

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53390

Middle Eastern (MID)

AF:

0.00243

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000630

AC:

AN:

1111910

Other (OTH)

AF:

0.00520

AC:

314

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

213

426

639

852

1065

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

196

294

392

490

<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:

0.0229

AC:

3483

AN:

152308

Hom.:

132

Cov.:

AF XY:

0.0220

AC XY:

1641

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.0797

AC:

3309

AN:

41544

American (AMR)

AF:

0.00784

AC:

120

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.000621

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000294

AC:

AN:

68020

Other (OTH)

AF:

0.0142

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

175

350

526

701

876

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<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:

0.00797

Hom.:

Bravo

AF:

0.0257

ESP6500AA

AF:

0.0740

AC:

308

ESP6500EA

AF:

0.000358

AC:

ExAC

AF:

0.00679

AC:

821

Asia WGS

AF:

0.00520

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.11

T;T;T;T;.;T;T;T

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.54

.;.;.;.;T;T;.;T

MetaRNN

Benign

0.0022

T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

L;.;L;L;L;.;L;L

PhyloP100

1.9

PrimateAI

Benign

0.20

PROVEAN

Benign

-2.3

N;N;N;N;.;N;N;N

REVEL

Benign

0.045

Sift

Benign

0.064

T;T;T;T;.;T;T;T

Sift4G

Uncertain

0.040

D;T;D;D;T;T;D;D

Polyphen

0.33

B;P;B;B;.;P;B;B

Vest4

0.11

MVP

0.55

MPC

0.037

ClinPred

0.0091

GERP RS

2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.064

gMVP

0.26

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.53

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.53

Position offset: 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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over