Genetic Variant IL18R1:c.-28-65C>T (chr2-102362568-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 NM_003855.5(IL18R1):c.-28-65C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 1,071,898 control chromosomes in the GnomAD database, including 77,870 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 0.34 ( 9015 hom., cov: 32)

Exomes 𝑓: 0.38 ( 68855 hom. )

Consequence

IL18R1
NM_003855.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.961

Publications

36 publications found

Variant links:

Genes affected

IL18R1 (HGNC:5988): (interleukin 18 receptor 1) The protein encoded by this gene is a cytokine receptor that belongs to the interleukin 1 receptor family. This receptor specifically binds interleukin 18 (IL18), and is essential for IL18 mediated signal transduction. IFN-alpha and IL12 are reported to induce the expression of this receptor in NK and T cells. This gene along with four other members of the interleukin 1 receptor family, including IL1R2, IL1R1, ILRL2 (IL-1Rrp2), and IL1RL1 (T1/ST2), form a gene cluster on chromosome 2q. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2013]

IL18R1 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=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL18R1	NM_003855.5 link	c.-28-65C>T		intron_variant	Intron 1 of 10	ENST00000233957.7	NP_003846.1	Q13478

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL18R1	ENST00000233957.7 link	c.-28-65C>T		intron_variant	Intron 1 of 10	5	NM_003855.5	ENSP00000233957.1		Q13478

Frequencies

GnomAD3 genomes

AF:

0.336

AC:

50929

AN:

151800

Hom.:

9014

Cov.:

show subpopulations

Gnomad AFR

AF:

0.235

Gnomad AMI

AF:

0.271

Gnomad AMR

AF:

0.290

Gnomad ASJ

AF:

0.307

Gnomad EAS

AF:

0.428

Gnomad SAS

AF:

0.356

Gnomad FIN

AF:

0.390

Gnomad MID

AF:

0.532

Gnomad NFE

AF:

0.391

Gnomad OTH

AF:

0.357

GnomAD4 exome

AF:

0.384

AC:

353486

AN:

919978

Hom.:

68855

AF XY:

0.385

AC XY:

179501

AN XY:

466710

show subpopulations

African (AFR)

AF:

0.233

AC:

4663

AN:

20054

American (AMR)

AF:

0.242

AC:

5543

AN:

22862

Ashkenazi Jewish (ASJ)

AF:

0.309

AC:

5346

AN:

17280

East Asian (EAS)

AF:

0.401

AC:

13401

AN:

33422

South Asian (SAS)

AF:

0.370

AC:

18420

AN:

49834

European-Finnish (FIN)

AF:

0.396

AC:

18594

AN:

47000

Middle Eastern (MID)

AF:

0.500

AC:

2185

AN:

4374

European-Non Finnish (NFE)

AF:

0.394

AC:

270037

AN:

684980

Other (OTH)

AF:

0.381

AC:

15297

AN:

40172

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

10508

21015

31523

42030

52538

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7648

15296

22944

30592

38240

<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:

0.335

AC:

50957

AN:

151920

Hom.:

9015

Cov.:

AF XY:

0.336

AC XY:

24938

AN XY:

74246

show subpopulations

African (AFR)

AF:

0.234

AC:

9706

AN:

41402

American (AMR)

AF:

0.290

AC:

4427

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.307

AC:

1065

AN:

3472

East Asian (EAS)

AF:

0.428

AC:

2210

AN:

5164

South Asian (SAS)

AF:

0.357

AC:

1723

AN:

4820

European-Finnish (FIN)

AF:

0.390

AC:

4105

AN:

10534

Middle Eastern (MID)

AF:

0.528

AC:

153

AN:

290

European-Non Finnish (NFE)

AF:

0.391

AC:

26556

AN:

67942

Other (OTH)

AF:

0.363

AC:

765

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1744

3488

5232

6976

8720

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

508

1016

1524

2032

2540

<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:

0.362

Hom.:

12454

Bravo

AF:

0.321

Asia WGS

AF:

0.410

AC:

1426

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.2

(source)

DANN

Benign

0.45

PhyloP100

-0.96

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