Genetic Variant ENST00000259206.9:c.11-105G>C (chr2-113119961-G-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000259206.9(IL1RN):c.11-105G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 880,292 control chromosomes in the GnomAD database, including 30,123 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 4065 hom., cov: 30)

Exomes 𝑓: 0.26 ( 26058 hom. )

Consequence

IL1RN
ENST00000259206.9 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.00600

Publications

2 publications found

Variant links:

Genes affected

IL1RN (HGNC:6000): (interleukin 1 receptor antagonist) The protein encoded by this gene is a member of the interleukin 1 cytokine family. This protein inhibits the activities of interleukin 1, alpha (IL1A) and interleukin 1, beta (IL1B), and modulates a variety of interleukin 1 related immune and inflammatory responses, particularly in the acute phase of infection and inflammation. This gene and five other closely related cytokine genes form a gene cluster spanning approximately 400 kb on chromosome 2. A polymorphism of this gene is reported to be associated with increased risk of osteoporotic fractures and gastric cancer. Several alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Aug 2020]

IL1RN Gene-Disease associations (from GenCC):

sterile multifocal osteomyelitis with periostitis and pustulosis
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics, Orphanet

IL1RN 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 (BayesDel_noAF=-0.87).

BP6

Variant 2-113119961-G-C is Benign according to our data. Variant chr2-113119961-G-C is described in ClinVar as Benign. ClinVar VariationId is 1241633.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000259206.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
IL1RN	NM_173841.3	c.11-105G>C	intron	N/A	NP_776213.1	P18510-3
IL1RN	NM_000577.5	c.10+1933G>C	intron	N/A	NP_000568.1	P18510-2
IL1RN	NM_001318914.2	c.-272-105G>C	intron	N/A	NP_001305843.1	P18510-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IL1RN	ENST00000259206.9	TSL:1	c.11-105G>C	intron	N/A	ENSP00000259206.5	P18510-3
IL1RN	ENST00000354115.6	TSL:1	c.10+1933G>C	intron	N/A	ENSP00000329072.3	P18510-2
IL1RN	ENST00000361779.7	TSL:1	c.-209-1487G>C	intron	N/A	ENSP00000354816.3	P18510-4

Frequencies

GnomAD3 genomes

AF:

0.209

AC:

31650

AN:

151734

Hom.:

4059

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0581

Gnomad AMI

AF:

0.246

Gnomad AMR

AF:

0.275

Gnomad ASJ

AF:

0.287

Gnomad EAS

AF:

0.0988

Gnomad SAS

AF:

0.283

Gnomad FIN

AF:

0.304

Gnomad MID

AF:

0.217

Gnomad NFE

AF:

0.269

Gnomad OTH

AF:

0.230

GnomAD4 exome

AF:

0.260

AC:

189488

AN:

728438

Hom.:

26058

AF XY:

0.261

AC XY:

99931

AN XY:

383356

show subpopulations

African (AFR)

AF:

0.0526

AC:

987

AN:

18770

American (AMR)

AF:

0.314

AC:

11042

AN:

35220

Ashkenazi Jewish (ASJ)

AF:

0.289

AC:

6059

AN:

20996

East Asian (EAS)

AF:

0.0832

AC:

2727

AN:

32784

South Asian (SAS)

AF:

0.277

AC:

18404

AN:

66520

European-Finnish (FIN)

AF:

0.297

AC:

14806

AN:

49810

Middle Eastern (MID)

AF:

0.210

AC:

900

AN:

4280

European-Non Finnish (NFE)

AF:

0.271

AC:

125580

AN:

464068

Other (OTH)

AF:

0.250

AC:

8983

AN:

35990

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

6823

13647

20470

27294

34117

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2272

4544

6816

9088

11360

<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:

0.209

AC:

31665

AN:

151854

Hom.:

4065

Cov.:

AF XY:

0.211

AC XY:

15668

AN XY:

74170

show subpopulations

African (AFR)

AF:

0.0579

AC:

2402

AN:

41466

American (AMR)

AF:

0.275

AC:

4199

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.287

AC:

994

AN:

3468

East Asian (EAS)

AF:

0.0983

AC:

507

AN:

5160

South Asian (SAS)

AF:

0.284

AC:

1361

AN:

4798

European-Finnish (FIN)

AF:

0.304

AC:

3190

AN:

10488

Middle Eastern (MID)

AF:

0.216

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.269

AC:

18239

AN:

67926

Other (OTH)

AF:

0.232

AC:

486

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1185

2370

3556

4741

5926

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

348

696

1044

1392

1740

<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:

0.235

Hom.:

646

Bravo

AF:

0.198

Asia WGS

AF:

0.196

AC:

683

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.6

(source)

DANN

Benign

0.50

PhyloP100

0.0060

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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