2-102340744-G-A

Position:

chr2-102340744-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_016232.5(IL1RL1):c.526G>A(p.Ala176Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00253 in 1,597,556 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0031 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 18 hom. )

Consequence

IL1RL1
NM_016232.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.21

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:

IL1RL1 (HGNC:):

IL1RL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0069009066).

BP6

Variant 2-102340744-G-A is Benign according to our data. Variant chr2-102340744-G-A is described in ClinVar as [Benign]. Clinvar id is 1629553.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00307 (468/152338) while in subpopulation EAS AF= 0.0322 (167/5192). AF 95% confidence interval is 0.0282. There are 3 homozygotes in gnomad4. There are 233 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL1RL1	NM_016232.5 linkuse as main transcript	c.526G>A	p.Ala176Thr	missense_variant	5/11	ENST00000233954.6	NP_057316.3	Q01638-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL1RL1	ENST00000233954.6 linkuse as main transcript	c.526G>A	p.Ala176Thr	missense_variant	5/11	1	NM_016232.5	ENSP00000233954.1		Q01638-1

Frequencies

GnomAD3 genomes

AF:

0.00307

AC:

468

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00164

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00223

Gnomad ASJ

AF:

0.0153

Gnomad EAS

AF:

0.0321

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00170

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00420

AC:

987

AN:

234962

Hom.:

AF XY:

0.00395

AC XY:

505

AN XY:

127756

show subpopulations

Gnomad AFR exome

AF:

0.00145

Gnomad AMR exome

AF:

0.00104

Gnomad ASJ exome

AF:

0.0118

Gnomad EAS exome

AF:

0.0294

Gnomad SAS exome

AF:

0.00242

Gnomad FIN exome

AF:

0.000419

Gnomad NFE exome

AF:

0.00212

Gnomad OTH exome

AF:

0.00423

GnomAD4 exome

AF:

0.00248

AC:

3579

AN:

1445218

Hom.:

Cov.:

AF XY:

0.00247

AC XY:

1775

AN XY:

719232

show subpopulations

Gnomad4 AFR exome

AF:

0.00264

Gnomad4 AMR exome

AF:

0.00112

Gnomad4 ASJ exome

AF:

0.0113

Gnomad4 EAS exome

AF:

0.0265

Gnomad4 SAS exome

AF:

0.00259

Gnomad4 FIN exome

AF:

0.000450

Gnomad4 NFE exome

AF:

0.00146

Gnomad4 OTH exome

AF:

0.00372

GnomAD4 genome

AF:

0.00307

AC:

468

AN:

152338

Hom.:

Cov.:

AF XY:

0.00313

AC XY:

233

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.00171

Gnomad4 AMR

AF:

0.00222

Gnomad4 ASJ

AF:

0.0153

Gnomad4 EAS

AF:

0.0322

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00171

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00364

Hom.:

Bravo

AF:

0.00385

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00295

AC:

ESP6500EA

AF:

0.00163

AC:

ExAC

AF:

0.00463

AC:

562

Asia WGS

AF:

0.00808

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 05, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.27

DANN

Benign

0.70

DEOGEN2

Benign

0.061

.;T;.;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.70

T;T;T;T

MetaRNN

Benign

0.0069

T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.080

.;N;N;.

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.30

N;N;N;N

REVEL

Benign

0.052

Sift

Benign

0.28

T;T;T;T

Sift4G

Benign

0.86

T;T;T;T

Polyphen

0.14, 0.22

.;B;B;.

Vest4

0.082

MVP

0.19

MPC

0.011

ClinPred

0.0019

GERP RS

-4.0

Varity_R

0.11

gMVP

0.44

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over