Genetic Variant IL1RN:c.205+431A>T (chr2-113130095-A-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_173842.3(IL1RN):c.205+431A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000263 in 152,178 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

IL1RN
NM_173842.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.169

Publications

7 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173842.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IL1RN	NM_173842.3	MANE Select	c.205+431A>T	intron	N/A	NP_776214.1	P18510-1
IL1RN	NM_173841.3		c.214+431A>T	intron	N/A	NP_776213.1	P18510-3
IL1RN	NM_000577.5		c.151+431A>T	intron	N/A	NP_000568.1	P18510-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IL1RN	ENST00000409930.4	TSL:1 MANE Select	c.205+431A>T	intron	N/A	ENSP00000387173.3	P18510-1
IL1RN	ENST00000259206.9	TSL:1	c.214+431A>T	intron	N/A	ENSP00000259206.5	P18510-3
IL1RN	ENST00000354115.6	TSL:1	c.151+431A>T	intron	N/A	ENSP00000329072.3	P18510-2

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000479

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

41692

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

21680

African (AFR)

AF:

0.00

AC:

AN:

2426

American (AMR)

AF:

0.00

AC:

AN:

3640

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

906

East Asian (EAS)

AF:

0.00

AC:

AN:

3448

South Asian (SAS)

AF:

0.00

AC:

AN:

4884

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1016

Middle Eastern (MID)

AF:

0.00

AC:

AN:

166

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

23218

Other (OTH)

AF:

0.00

AC:

AN:

1988

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41542

American (AMR)

AF:

0.00

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10568

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67986

Other (OTH)

AF:

0.000474

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

613

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

2.6

(source)

DANN

Benign

0.40

PhyloP100

0.17

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over