ENST00000427077.1:n.*492G>A – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B.

-12

BP4_StrongBA1

The ENST00000427077.1(IL1RL1):n.*492G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 1,564,902 control chromosomes in the GnomAD database, including 59,315 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 0.22 ( 4269 hom., cov: 33)

Exomes 𝑓: 0.28 ( 55046 hom. )

Consequence

IL1RL1
ENST00000427077.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.638

Publications

27 publications found

Variant links:

Genes affected

IL1RL1 (HGNC:5998): (interleukin 1 receptor like 1) The protein encoded by this gene is a member of the interleukin 1 receptor family. Studies of the similar gene in mouse suggested that this receptor can be induced by proinflammatory stimuli, and may be involved in the function of helper T cells. This gene, interleukin 1 receptor, type I (IL1R1), interleukin 1 receptor, type II (IL1R2) and interleukin 1 receptor-like 2 (IL1RL2) form a cytokine receptor gene cluster in a region mapped to chromosome 2q12. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2008]

IL1RL1 links:

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=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1RL1	NM_016232.5 link	c.970+132G>A		intron_variant	Intron 8 of 10	ENST00000233954.6	NP_057316.3	Q01638-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1RL1	ENST00000233954.6 link	c.970+132G>A		intron_variant	Intron 8 of 10	1	NM_016232.5	ENSP00000233954.1		Q01638-1

Frequencies

GnomAD3 genomes

AF:

0.218

AC:

33119

AN:

152028

Hom.:

4268

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0971

Gnomad AMI

AF:

0.184

Gnomad AMR

AF:

0.180

Gnomad ASJ

AF:

0.151

Gnomad EAS

AF:

0.393

Gnomad SAS

AF:

0.277

Gnomad FIN

AF:

0.264

Gnomad MID

AF:

0.231

Gnomad NFE

AF:

0.279

Gnomad OTH

AF:

0.211

GnomAD4 exome

AF:

0.275

AC:

388876

AN:

1412756

Hom.:

55046

Cov.:

AF XY:

0.276

AC XY:

192699

AN XY:

698234

show subpopulations

African (AFR)

AF:

0.0870

AC:

2833

AN:

32556

American (AMR)

AF:

0.163

AC:

6694

AN:

41086

Ashkenazi Jewish (ASJ)

AF:

0.153

AC:

3595

AN:

23548

East Asian (EAS)

AF:

0.387

AC:

15204

AN:

39258

South Asian (SAS)

AF:

0.283

AC:

22557

AN:

79580

European-Finnish (FIN)

AF:

0.272

AC:

11623

AN:

42770

Middle Eastern (MID)

AF:

0.173

AC:

864

AN:

4988

European-Non Finnish (NFE)

AF:

0.285

AC:

310260

AN:

1090362

Other (OTH)

AF:

0.260

AC:

15246

AN:

58608

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

14083

28167

42250

56334

70417

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10496

20992

31488

41984

52480

<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:

0.218

AC:

33126

AN:

152146

Hom.:

4269

Cov.:

AF XY:

0.218

AC XY:

16183

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.0969

AC:

4026

AN:

41542

American (AMR)

AF:

0.180

AC:

2746

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.151

AC:

523

AN:

3468

East Asian (EAS)

AF:

0.394

AC:

2031

AN:

5158

South Asian (SAS)

AF:

0.278

AC:

1339

AN:

4822

European-Finnish (FIN)

AF:

0.264

AC:

2788

AN:

10576

Middle Eastern (MID)

AF:

0.214

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.279

AC:

18982

AN:

67976

Other (OTH)

AF:

0.218

AC:

461

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1303

2606

3910

5213

6516

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

366

732

1098

1464

1830

<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:

0.197

Hom.:

1851

Bravo

AF:

0.204

Asia WGS

AF:

0.339

AC:

1181

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.10

(source)

DANN

Benign

0.47

PhyloP100

-0.64

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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