dbSNP rs3218984: IL1R2:c.1031-227T>C (chr2-102027999-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004633.4(IL1R2):c.1031-227T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 152,052 control chromosomes in the GnomAD database, including 5,459 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 0.26 ( 5459 hom., cov: 32)

Consequence

IL1R2
NM_004633.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.07

Publications

7 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1R2	NM_004633.4 link	c.1031-227T>C		intron_variant	Intron 8 of 8	ENST00000332549.8	NP_004624.1	P27930-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
IL1R2	ENST00000332549.8 link	c.1031-227T>C	intron_variant	Intron 8 of 8	1	NM_004633.4	ENSP00000330959.3	P27930-1
IL1R2	ENST00000393414.6 link	c.1031-227T>C	intron_variant	Intron 8 of 8	1		ENSP00000377066.2	P27930-1
IL1R2	ENST00000474085.5 link	n.467-227T>C	intron_variant	Intron 3 of 3	2
IL1R2	ENST00000485335.1 link	n.512-227T>C	intron_variant	Intron 3 of 3	3

Frequencies

GnomAD3 genomes

AF:

0.262

AC:

39759

AN:

151932

Hom.:

5451

Cov.:

show subpopulations

Gnomad AFR

AF:

0.223

Gnomad AMI

AF:

0.252

Gnomad AMR

AF:

0.290

Gnomad ASJ

AF:

0.216

Gnomad EAS

AF:

0.261

Gnomad SAS

AF:

0.132

Gnomad FIN

AF:

0.413

Gnomad MID

AF:

0.209

Gnomad NFE

AF:

0.268

Gnomad OTH

AF:

0.258

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.262

AC:

39800

AN:

152052

Hom.:

5459

Cov.:

AF XY:

0.266

AC XY:

19782

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.223

AC:

9238

AN:

41474

American (AMR)

AF:

0.290

AC:

4433

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.216

AC:

749

AN:

3472

East Asian (EAS)

AF:

0.261

AC:

1348

AN:

5164

South Asian (SAS)

AF:

0.132

AC:

637

AN:

4816

European-Finnish (FIN)

AF:

0.413

AC:

4349

AN:

10536

Middle Eastern (MID)

AF:

0.221

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.268

AC:

18210

AN:

67986

Other (OTH)

AF:

0.256

AC:

541

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1505

3010

4515

6020

7525

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.261

Hom.:

2779

Bravo

AF:

0.256

Asia WGS

AF:

0.197

AC:

688

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.020

(source)

DANN

Benign

0.18

PhyloP100

-2.1

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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rs3218984

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over