Genetic Variant IL1RL1:p.Asn455Asn (chr2-102351615-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_016232.5(IL1RL1):c.1365T>C(p.Asn455Asn) 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 1,613,674 control chromosomes in the GnomAD database, including 122,805 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 0.45 ( 17753 hom., cov: 31)

Exomes 𝑓: 0.37 ( 105052 hom. )

Consequence

IL1RL1
NM_016232.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.201

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 made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP7

Synonymous conserved (PhyloP=0.201 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.1365T>C	p.Asn455Asn	synonymous_variant	Exon 11 of 11	ENST00000233954.6	NP_057316.3	Q01638-1
IL1RL1	XM_006712839.4 link	c.1365T>C	p.Asn455Asn	synonymous_variant	Exon 11 of 11		XP_006712902.1	Q01638-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1RL1	ENST00000233954.6 link	c.1365T>C	p.Asn455Asn	synonymous_variant	Exon 11 of 11	1	NM_016232.5	ENSP00000233954.1		Q01638-1
IL18R1	ENST00000410040.5 link	c.-28-11018T>C		intron_variant	Intron 1 of 10	2		ENSP00000386663.1		Q13478

Frequencies

GnomAD3 genomes

AF:

0.452

AC:

68602

AN:

151876

Hom.:

17724

Cov.:

show subpopulations

Gnomad AFR

AF:

0.702

Gnomad AMI

AF:

0.404

Gnomad AMR

AF:

0.318

Gnomad ASJ

AF:

0.477

Gnomad EAS

AF:

0.128

Gnomad SAS

AF:

0.200

Gnomad FIN

AF:

0.423

Gnomad MID

AF:

0.244

Gnomad NFE

AF:

0.378

Gnomad OTH

AF:

0.416

GnomAD3 exomes

AF:

0.341

AC:

85769

AN:

251318

Hom.:

17341

AF XY:

0.332

AC XY:

45086

AN XY:

135820

show subpopulations

Gnomad AFR exome

AF:

0.710

Gnomad AMR exome

AF:

0.218

Gnomad ASJ exome

AF:

0.462

Gnomad EAS exome

AF:

0.116

Gnomad SAS exome

AF:

0.179

Gnomad FIN exome

AF:

0.416

Gnomad NFE exome

AF:

0.379

Gnomad OTH exome

AF:

0.371

GnomAD4 exome

AF:

0.368

AC:

538625

AN:

1461680

Hom.:

105052

Cov.:

AF XY:

0.362

AC XY:

263295

AN XY:

727144

show subpopulations

Gnomad4 AFR exome

AF:

0.714

Gnomad4 AMR exome

AF:

0.230

Gnomad4 ASJ exome

AF:

0.469

Gnomad4 EAS exome

AF:

0.151

Gnomad4 SAS exome

AF:

0.183

Gnomad4 FIN exome

AF:

0.414

Gnomad4 NFE exome

AF:

0.382

Gnomad4 OTH exome

AF:

0.371

GnomAD4 genome

AF:

0.452

AC:

68681

AN:

151994

Hom.:

17753

Cov.:

AF XY:

0.445

AC XY:

33039

AN XY:

74274

show subpopulations

Gnomad4 AFR

AF:

0.702

Gnomad4 AMR

AF:

0.318

Gnomad4 ASJ

AF:

0.477

Gnomad4 EAS

AF:

0.128

Gnomad4 SAS

AF:

0.199

Gnomad4 FIN

AF:

0.423

Gnomad4 NFE

AF:

0.378

Gnomad4 OTH

AF:

0.412

Alfa

AF:

0.384

Hom.:

15421

Bravo

AF:

0.457

Asia WGS

AF:

0.180

AC:

627

AN:

3478

EpiCase

AF:

0.380

EpiControl

AF:

0.383

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

2.5

DANN

Benign

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over