2-102340676-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_016232.5(IL1RL1):c.458C>T(p.Ala153Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00122 in 1,585,866 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0066 ( 18 hom., cov: 32)

Exomes 𝑓: 0.00064 ( 9 hom. )

Consequence

IL1RL1
NM_016232.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0980

Publications

3 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0034545958).

BP6

Variant 2-102340676-C-T is Benign according to our data. Variant chr2-102340676-C-T is described in ClinVar as [Benign]. Clinvar id is 769571.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00661 (1006/152262) while in subpopulation AFR AF = 0.0227 (941/41536). AF 95% confidence interval is 0.0215. There are 18 homozygotes in GnomAd4. There are 501 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1RL1	NM_016232.5 link	c.458C>T	p.Ala153Val	missense_variant	Exon 5 of 11	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.458C>T	p.Ala153Val	missense_variant	Exon 5 of 11	1	NM_016232.5	ENSP00000233954.1		Q01638-1

Frequencies

GnomAD3 genomes

AF:

0.00655

AC:

997

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0225

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00334

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00574

GnomAD2 exomes

AF:

0.00162

AC:

360

AN:

222556

AF XY:

0.00121

show subpopulations

Gnomad AFR exome

AF:

0.0217

Gnomad AMR exome

AF:

0.00102

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000474

Gnomad OTH exome

AF:

0.000929

GnomAD4 exome

AF:

0.000643

AC:

922

AN:

1433604

Hom.:

Cov.:

AF XY:

0.000544

AC XY:

388

AN XY:

713174

show subpopulations

African (AFR)

AF:

0.0240

AC:

750

AN:

31222

American (AMR)

AF:

0.00132

AC:

AN:

35516

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25012

East Asian (EAS)

AF:

0.00

AC:

AN:

38550

South Asian (SAS)

AF:

0.0000247

AC:

AN:

80836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53218

Middle Eastern (MID)

AF:

0.000528

AC:

AN:

5684

European-Non Finnish (NFE)

AF:

0.0000217

AC:

AN:

1104324

Other (OTH)

AF:

0.00162

AC:

AN:

59242

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

133

178

222

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00661

AC:

1006

AN:

152262

Hom.:

Cov.:

AF XY:

0.00673

AC XY:

501

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.0227

AC:

941

AN:

41536

American (AMR)

AF:

0.00334

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68024

Other (OTH)

AF:

0.00568

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

100

150

200

250

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00255

Hom.:

Bravo

AF:

0.00795

ESP6500AA

AF:

0.0209

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00203

AC:

247

Asia WGS

AF:

0.00289

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.75

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.078

.;T;.;T

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.091

LIST_S2

Benign

0.71

T;T;T;T

MetaRNN

Benign

0.0035

T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.55

.;N;N;.

PhyloP100

0.098

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.2

N;N;N;N

REVEL

Benign

0.036

Sift

Benign

0.50

T;T;T;T

Sift4G

Benign

0.74

T;T;T;T

Polyphen

0.034, 0.056

.;B;B;.

Vest4

0.20

MVP

0.24

MPC

0.011

ClinPred

0.0031

GERP RS

1.9

Varity_R

0.064

gMVP

0.34

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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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2-102340676-C-T

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