Genetic Variant ENST00000259206.9:c.11-821T>G (chr2-113119245-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000259206.9(IL1RN):c.11-821T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.962 in 152,266 control chromosomes in the GnomAD database, including 70,749 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 0.96 ( 70749 hom., cov: 31)

Consequence

IL1RN
ENST00000259206.9 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.23

Publications

3 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: Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

IL1RN links:

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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=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 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
IL1RN	NM_173841.3	c.11-821T>G	intron	N/A	NP_776213.1
IL1RN	NM_000577.5	c.10+1217T>G	intron	N/A	NP_000568.1
IL1RN	NM_001318914.2	c.-272-821T>G	intron	N/A	NP_001305843.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
IL1RN	ENST00000259206.9	TSL:1	c.11-821T>G	intron	N/A	ENSP00000259206.5
IL1RN	ENST00000354115.6	TSL:1	c.10+1217T>G	intron	N/A	ENSP00000329072.3
IL1RN	ENST00000361779.7	TSL:1	c.-210+1217T>G	intron	N/A	ENSP00000354816.3

Frequencies

GnomAD3 genomes

AF:

0.962

AC:

146423

AN:

152148

Hom.:

70697

Cov.:

show subpopulations

Gnomad AFR

AF:

0.871

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.983

Gnomad ASJ

AF:

0.997

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.994

Gnomad NFE

AF:

0.999

Gnomad OTH

AF:

0.974

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

GnomAD4 genome

AF:

0.962

AC:

146532

AN:

152266

Hom.:

70749

Cov.:

AF XY:

0.964

AC XY:

71741

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.871

AC:

36148

AN:

41510

American (AMR)

AF:

0.983

AC:

15035

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.997

AC:

3461

AN:

3472

East Asian (EAS)

AF:

1.00

AC:

5180

AN:

5180

South Asian (SAS)

AF:

1.00

AC:

4830

AN:

4832

European-Finnish (FIN)

AF:

1.00

AC:

10622

AN:

10622

Middle Eastern (MID)

AF:

0.997

AC:

293

AN:

294

European-Non Finnish (NFE)

AF:

0.999

AC:

67989

AN:

68026

Other (OTH)

AF:

0.974

AC:

2062

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

261

522

782

1043

1304

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

912

1824

2736

3648

4560

<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:

0.976

Hom.:

92686

Bravo

AF:

0.957

Asia WGS

AF:

0.992

AC:

3450

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.74

(source)

DANN

Benign

0.51

PhyloP100

-1.2

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over