Variant 2-113118054-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000259206.9(IL1RN):c.10+26T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 1,608,216 control chromosomes in the GnomAD database, including 56,563 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 4097 hom., cov: 33)

Exomes 𝑓: 0.26 ( 52466 hom. )

Consequence

IL1RN
ENST00000259206.9 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.703

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

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

BP6

Variant 2-113118054-T-C is Benign according to our data. Variant chr2-113118054-T-C is described in ClinVar as [Benign]. Clinvar id is 1244315.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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Protein
IL1RN	NM_000577.5 linkuse as main transcript	c.10+26T>C	intron_variant	NP_000568.1
IL1RN	NM_001318914.2 linkuse as main transcript	c.-273+26T>C	intron_variant	NP_001305843.1
IL1RN	NM_173841.3 linkuse as main transcript	c.10+26T>C	intron_variant	NP_776213.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	Protein	Appris	UniProt
IL1RN	ENST00000259206.9 linkuse as main transcript	c.10+26T>C	intron_variant	1	ENSP00000259206		P18510-3
IL1RN	ENST00000354115.6 linkuse as main transcript	c.10+26T>C	intron_variant	1	ENSP00000329072	A1	P18510-2
IL1RN	ENST00000361779.7 linkuse as main transcript	c.-210+26T>C	intron_variant	1	ENSP00000354816		P18510-4

Frequencies

GnomAD3 genomes

AF:

0.209

AC:

31842

AN:

152112

Hom.:

4091

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0583

Gnomad AMI

AF:

0.244

Gnomad AMR

AF:

0.277

Gnomad ASJ

AF:

0.293

Gnomad EAS

AF:

0.0971

Gnomad SAS

AF:

0.283

Gnomad FIN

AF:

0.305

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.269

Gnomad OTH

AF:

0.231

GnomAD3 exomes

AF:

0.253

AC:

63648

AN:

251392

Hom.:

9031

AF XY:

0.256

AC XY:

34797

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.0510

Gnomad AMR exome

AF:

0.321

Gnomad ASJ exome

AF:

0.300

Gnomad EAS exome

AF:

0.0924

Gnomad SAS exome

AF:

0.281

Gnomad FIN exome

AF:

0.304

Gnomad NFE exome

AF:

0.266

Gnomad OTH exome

AF:

0.265

GnomAD4 exome

AF:

0.261

AC:

380615

AN:

1455984

Hom.:

52466

Cov.:

AF XY:

0.261

AC XY:

189326

AN XY:

724622

show subpopulations

Gnomad4 AFR exome

AF:

0.0467

Gnomad4 AMR exome

AF:

0.315

Gnomad4 ASJ exome

AF:

0.290

Gnomad4 EAS exome

AF:

0.0834

Gnomad4 SAS exome

AF:

0.278

Gnomad4 FIN exome

AF:

0.296

Gnomad4 NFE exome

AF:

0.269

Gnomad4 OTH exome

AF:

0.251

GnomAD4 genome

AF:

0.209

AC:

31857

AN:

152232

Hom.:

4097

Cov.:

AF XY:

0.212

AC XY:

15801

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.0581

Gnomad4 AMR

AF:

0.278

Gnomad4 ASJ

AF:

0.293

Gnomad4 EAS

AF:

0.0965

Gnomad4 SAS

AF:

0.284

Gnomad4 FIN

AF:

0.305

Gnomad4 NFE

AF:

0.269

Gnomad4 OTH

AF:

0.233

Alfa

AF:

0.247

Hom.:

1601

Bravo

AF:

0.199

Asia WGS

AF:

0.195

AC:

679

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 12, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Nov 12, 2023

This variant is classified as Benign based on local population frequency. This variant was detected in 49% of patients studied by a panel of primary immunodeficiencies. Number of patients: 47. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

2.6

DANN

Benign

0.65

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over