NM_004633.4:c.541G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_004633.4(IL1R2):c.541G>A(p.Glu181Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00345 in 1,612,828 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0026 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0035 ( 8 hom. )

Consequence

IL1R2
NM_004633.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.524

Publications

8 publications found

Variant links:

Genes affected

IL1R2 (HGNC:5994): (interleukin 1 receptor type 2) The protein encoded by this gene is a cytokine receptor that belongs to the interleukin 1 receptor family. This protein binds interleukin alpha (IL1A), interleukin beta (IL1B), and interleukin 1 receptor, type I(IL1R1/IL1RA), and acts as a decoy receptor that inhibits the activity of its ligands. Interleukin 4 (IL4) is reported to antagonize the activity of interleukin 1 by inducing the expression and release of this cytokine. This gene and three other genes form a cytokine receptor gene cluster on chromosome 2q12. Alternative splicing results in multiple transcript variants and protein isoforms. Alternative splicing produces both membrane-bound and soluble proteins. A soluble protein is also produced by proteolytic cleavage. [provided by RefSeq, May 2012]

IL1R2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0030221045).

BP6

Variant 2-102019665-G-A is Benign according to our data. Variant chr2-102019665-G-A is described in ClinVar as Benign. ClinVar VariationId is 711193.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004633.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IL1R2	NM_004633.4	MANE Select	c.541G>A	p.Glu181Lys	missense	Exon 5 of 9	NP_004624.1	P27930-1
IL1R2	NM_001261419.2		c.541G>A	p.Glu181Lys	missense	Exon 5 of 7	NP_001248348.1	P27930-2
IL1R2	NR_048564.2		n.758G>A		non_coding_transcript_exon	Exon 5 of 9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IL1R2	ENST00000332549.8	TSL:1 MANE Select	c.541G>A	p.Glu181Lys	missense	Exon 5 of 9	ENSP00000330959.3	P27930-1
IL1R2	ENST00000393414.6	TSL:1	c.541G>A	p.Glu181Lys	missense	Exon 5 of 9	ENSP00000377066.2	P27930-1
IL1R2	ENST00000441002.1	TSL:1	c.541G>A	p.Glu181Lys	missense	Exon 4 of 6	ENSP00000414611.1	P27930-2

Frequencies

GnomAD3 genomes

AF:

0.00258

AC:

392

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00735

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00398

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00260

AC:

651

AN:

250120

AF XY:

0.00251

show subpopulations

Gnomad AFR exome

AF:

0.000555

Gnomad AMR exome

AF:

0.000263

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00740

Gnomad NFE exome

AF:

0.00378

Gnomad OTH exome

AF:

0.00262

GnomAD4 exome

AF:

0.00354

AC:

5173

AN:

1460542

Hom.:

Cov.:

AF XY:

0.00349

AC XY:

2539

AN XY:

726518

show subpopulations

African (AFR)

AF:

0.000718

AC:

AN:

33436

American (AMR)

AF:

0.000270

AC:

AN:

44454

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26084

East Asian (EAS)

AF:

0.00

AC:

AN:

39688

South Asian (SAS)

AF:

0.000931

AC:

AN:

85928

European-Finnish (FIN)

AF:

0.00734

AC:

392

AN:

53414

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00407

AC:

4521

AN:

1111416

Other (OTH)

AF:

0.00234

AC:

141

AN:

60354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

228

456

685

913

1141

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

180

360

540

720

900

<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:

0.00257

AC:

392

AN:

152286

Hom.:

Cov.:

AF XY:

0.00247

AC XY:

184

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.000505

AC:

AN:

41552

American (AMR)

AF:

0.000850

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.000621

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00735

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00398

AC:

271

AN:

68022

Other (OTH)

AF:

0.00284

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00957

Hom.:

821

Bravo

AF:

0.00194

TwinsUK

AF:

0.00431

AC:

ALSPAC

AF:

0.00415

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00349

AC:

ExAC

AF:

0.00247

AC:

300

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00273

EpiControl

AF:

0.00338

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.60

CADD

Benign

0.89

(source)

DANN

Benign

0.65

DEOGEN2

Benign

0.10

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0093

LIST_S2

Benign

0.68

M_CAP

Benign

0.0078

MetaRNN

Benign

0.0030

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.32

PhyloP100

-0.52

PrimateAI

Benign

0.20

PROVEAN

Benign

0.56

REVEL

Benign

0.051

Sift

Benign

0.83

Sift4G

Benign

0.64

Polyphen

0.0070

Vest4

0.071

MVP

0.12

MPC

0.11

ClinPred

0.0027

GERP RS

-8.3

Varity_R

0.12

gMVP

0.46

Mutation Taster

=98/2

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over