Genetic Variant NM_016232.5:c.1575T>C (chr2-102351825-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_016232.5(IL1RL1):c.1575T>C(p.Ser525Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 1,612,504 control chromosomes in the GnomAD database, including 122,739 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

Frequency

Genomes: 𝑓 0.45 ( 17710 hom., cov: 30)

Exomes 𝑓: 0.37 ( 105029 hom. )

Consequence

IL1RL1
NM_016232.5 synonymous

Scores

Clinical Significance

association no assertion criteria provided O:1

Conservation

PhyloP100: 0.158

Publications

41 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP7

Synonymous conserved (PhyloP=0.158 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1RL1	NM_016232.5 link	c.1575T>C	p.Ser525Ser	synonymous_variant	Exon 11 of 11	ENST00000233954.6	NP_057316.3
IL1RL1	XM_006712839.4 link	c.1575T>C	p.Ser525Ser	synonymous_variant	Exon 11 of 11		XP_006712902.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1RL1	ENST00000233954.6 link	c.1575T>C	p.Ser525Ser	synonymous_variant	Exon 11 of 11	1	NM_016232.5	ENSP00000233954.1
IL18R1	ENST00000410040.5 link	c.-28-10808T>C		intron_variant	Intron 1 of 10	2		ENSP00000386663.1

Frequencies

GnomAD3 genomes

AF:

0.451

AC:

68490

AN:

151754

Hom.:

17681

Cov.:

show subpopulations

Gnomad AFR

AF:

0.701

Gnomad AMI

AF:

0.404

Gnomad AMR

AF:

0.318

Gnomad ASJ

AF:

0.477

Gnomad EAS

AF:

0.127

Gnomad SAS

AF:

0.200

Gnomad FIN

AF:

0.421

Gnomad MID

AF:

0.242

Gnomad NFE

AF:

0.378

Gnomad OTH

AF:

0.413

GnomAD2 exomes

AF:

0.341

AC:

85650

AN:

251140

AF XY:

0.332

show subpopulations

Gnomad AFR exome

AF:

0.709

Gnomad AMR exome

AF:

0.218

Gnomad ASJ exome

AF:

0.462

Gnomad EAS exome

AF:

0.115

Gnomad FIN exome

AF:

0.416

Gnomad NFE exome

AF:

0.379

Gnomad OTH exome

AF:

0.370

GnomAD4 exome

AF:

0.368

AC:

538094

AN:

1460630

Hom.:

105029

Cov.:

AF XY:

0.362

AC XY:

263069

AN XY:

726690

show subpopulations

African (AFR)

AF:

0.714

AC:

23877

AN:

33456

American (AMR)

AF:

0.230

AC:

10269

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.469

AC:

12244

AN:

26132

East Asian (EAS)

AF:

0.150

AC:

5966

AN:

39660

South Asian (SAS)

AF:

0.183

AC:

15814

AN:

86234

European-Finnish (FIN)

AF:

0.415

AC:

22127

AN:

53382

Middle Eastern (MID)

AF:

0.283

AC:

1632

AN:

5766

European-Non Finnish (NFE)

AF:

0.381

AC:

423770

AN:

1110916

Other (OTH)

AF:

0.371

AC:

22395

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

16862

33724

50587

67449

84311

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13184

26368

39552

52736

65920

<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:

0.451

AC:

68570

AN:

151874

Hom.:

17710

Cov.:

AF XY:

0.444

AC XY:

32981

AN XY:

74230

show subpopulations

African (AFR)

AF:

0.702

AC:

29057

AN:

41412

American (AMR)

AF:

0.318

AC:

4846

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.477

AC:

1656

AN:

3472

East Asian (EAS)

AF:

0.128

AC:

659

AN:

5162

South Asian (SAS)

AF:

0.199

AC:

961

AN:

4822

European-Finnish (FIN)

AF:

0.421

AC:

4443

AN:

10542

Middle Eastern (MID)

AF:

0.243

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.378

AC:

25650

AN:

67906

Other (OTH)

AF:

0.409

AC:

859

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1685

3370

5056

6741

8426

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

590

1180

1770

2360

2950

<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:

0.403

Hom.:

20889

Bravo

AF:

0.458

Asia WGS

AF:

0.180

AC:

627

AN:

3478

EpiCase

AF:

0.380

EpiControl

AF:

0.383

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Ascending aortic dissection

Other:1

Feb 01, 2021

Beijing Anzhen Hospital, Capital Medical University

Significance:association

Review Status:no assertion criteria provided

Collection Method:case-control

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

6.1

(source)

DANN

Benign

0.71

PhyloP100

0.16

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over