dbSNP rs3917320: IL1R1:p.Arg456Arg (chr2-102176415-A-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_000877.4(IL1R1):c.1366A>C(p.Arg456Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0473 in 1,614,118 control chromosomes in the GnomAD database, including 2,191 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 0.057 ( 310 hom., cov: 32)

Exomes 𝑓: 0.046 ( 1881 hom. )

Consequence

IL1R1
NM_000877.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.101

Publications

20 publications found

Variant links:

Genes affected

IL1R1 (HGNC:5993): (interleukin 1 receptor type 1) This gene encodes a cytokine receptor that belongs to the interleukin-1 receptor family. The encoded protein is a receptor for interleukin-1 alpha, interleukin-1 beta, and interleukin-1 receptor antagonist. It is an important mediator involved in many cytokine-induced immune and inflammatory responses. This gene is located in a cluster of related cytokine receptor genes on chromosome 2q12. [provided by RefSeq, Dec 2013]

IL1R1 links:

IL1R1-AS1 (HGNC:53898): (IL1R1 antisense RNA 1)

IL1R1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP7

Synonymous conserved (PhyloP=0.101 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0839 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1R1	NM_000877.4 link	c.1366A>C	p.Arg456Arg	synonymous_variant	Exon 12 of 12	ENST00000410023.6	NP_000868.1	P14778

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1R1	ENST00000410023.6 link	c.1366A>C	p.Arg456Arg	synonymous_variant	Exon 12 of 12	1	NM_000877.4	ENSP00000386380.1		P14778

Frequencies

GnomAD3 genomes

AF:

0.0567

AC:

8634

AN:

152198

Hom.:

311

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0863

Gnomad AMI

AF:

0.167

Gnomad AMR

AF:

0.0610

Gnomad ASJ

AF:

0.0657

Gnomad EAS

AF:

0.000769

Gnomad SAS

AF:

0.0116

Gnomad FIN

AF:

0.0185

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.0484

Gnomad OTH

AF:

0.0712

GnomAD2 exomes

AF:

0.0416

AC:

10443

AN:

251320

AF XY:

0.0404

show subpopulations

Gnomad AFR exome

AF:

0.0881

Gnomad AMR exome

AF:

0.0434

Gnomad ASJ exome

AF:

0.0680

Gnomad EAS exome

AF:

0.000435

Gnomad FIN exome

AF:

0.0144

Gnomad NFE exome

AF:

0.0506

Gnomad OTH exome

AF:

0.0566

GnomAD4 exome

AF:

0.0463

AC:

67736

AN:

1461800

Hom.:

1881

Cov.:

AF XY:

0.0455

AC XY:

33078

AN XY:

727198

show subpopulations

African (AFR)

AF:

0.0864

AC:

2894

AN:

33476

American (AMR)

AF:

0.0471

AC:

2108

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0679

AC:

1775

AN:

26134

East Asian (EAS)

AF:

0.000176

AC:

AN:

39694

South Asian (SAS)

AF:

0.0138

AC:

1191

AN:

86256

European-Finnish (FIN)

AF:

0.0144

AC:

769

AN:

53418

Middle Eastern (MID)

AF:

0.146

AC:

840

AN:

5768

European-Non Finnish (NFE)

AF:

0.0494

AC:

54979

AN:

1111938

Other (OTH)

AF:

0.0525

AC:

3173

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

3578

7157

10735

14314

17892

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2060

4120

6180

8240

10300

<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:

0.0567

AC:

8642

AN:

152318

Hom.:

310

Cov.:

AF XY:

0.0552

AC XY:

4114

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.0863

AC:

3586

AN:

41570

American (AMR)

AF:

0.0609

AC:

932

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0657

AC:

228

AN:

3470

East Asian (EAS)

AF:

0.000771

AC:

AN:

5188

South Asian (SAS)

AF:

0.0118

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0185

AC:

197

AN:

10624

Middle Eastern (MID)

AF:

0.146

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0484

AC:

3294

AN:

68016

Other (OTH)

AF:

0.0704

AC:

149

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

420

839

1259

1678

2098

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

184

276

368

460

<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:

0.0564

Hom.:

446

Bravo

AF:

0.0638

Asia WGS

AF:

0.0130

AC:

AN:

3478

EpiCase

AF:

0.0588

EpiControl

AF:

0.0596

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

6.6

(source)

DANN

Benign

0.72

PhyloP100

0.10

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over