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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003855.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IL18R1	NM_003855.5	MANE Select	c.-28-65C>T	intron	N/A	NP_003846.1	Q13478
IL18R1	NM_001371418.1		c.-28-65C>T	intron	N/A	NP_001358347.1	B7ZKV7
IL18R1	NM_001371419.1		c.-28-65C>T	intron	N/A	NP_001358348.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IL18R1	ENST00000233957.7	TSL:5 MANE Select	c.-28-65C>T	intron	N/A	ENSP00000233957.1	Q13478
IL18R1	ENST00000409599.5	TSL:5	c.-28-65C>T	intron	N/A	ENSP00000387211.1	Q13478
IL18R1	ENST00000410040.5	TSL:2	c.-28-65C>T	intron	N/A	ENSP00000386663.1	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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over