Variant rs432014 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 NM_173842.3(IL1RN):c.206-43T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 1,227,456 control chromosomes in the GnomAD database, including 44,853 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 4757 hom., cov: 31)

Exomes 𝑓: 0.27 ( 40096 hom. )

Consequence

IL1RN
NM_173842.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.313

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=-0.93).

BP6

Variant 2-113131002-T-C is Benign according to our data. Variant chr2-113131002-T-C is described in ClinVar as [Benign]. Clinvar id is 1294753.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1RN	NM_173842.3 linkuse as main transcript	c.206-43T>C		intron_variant		ENST00000409930.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1RN	ENST00000409930.4 linkuse as main transcript	c.206-43T>C		intron_variant		1	NM_173842.3	P4	P18510-1

Frequencies

GnomAD3 genomes

AF:

0.242

AC:

36823

AN:

151880

Hom.:

4746

Cov.:

show subpopulations

Gnomad AFR

AF:

0.165

Gnomad AMI

AF:

0.246

Gnomad AMR

AF:

0.292

Gnomad ASJ

AF:

0.291

Gnomad EAS

AF:

0.0777

Gnomad SAS

AF:

0.291

Gnomad FIN

AF:

0.303

Gnomad MID

AF:

0.229

Gnomad NFE

AF:

0.275

Gnomad OTH

AF:

0.255

GnomAD3 exomes

AF:

0.264

AC:

66127

AN:

250134

Hom.:

9455

AF XY:

0.265

AC XY:

35855

AN XY:

135226

show subpopulations

Gnomad AFR exome

AF:

0.164

Gnomad AMR exome

AF:

0.330

Gnomad ASJ exome

AF:

0.298

Gnomad EAS exome

AF:

0.0704

Gnomad SAS exome

AF:

0.289

Gnomad FIN exome

AF:

0.304

Gnomad NFE exome

AF:

0.273

Gnomad OTH exome

AF:

0.270

GnomAD4 exome

AF:

0.265

AC:

285406

AN:

1075458

Hom.:

40096

Cov.:

AF XY:

0.265

AC XY:

146700

AN XY:

552730

show subpopulations

Gnomad4 AFR exome

AF:

0.164

Gnomad4 AMR exome

AF:

0.326

Gnomad4 ASJ exome

AF:

0.290

Gnomad4 EAS exome

AF:

0.0594

Gnomad4 SAS exome

AF:

0.283

Gnomad4 FIN exome

AF:

0.299

Gnomad4 NFE exome

AF:

0.271

Gnomad4 OTH exome

AF:

0.259

GnomAD4 genome

AF:

0.243

AC:

36865

AN:

151998

Hom.:

4757

Cov.:

AF XY:

0.244

AC XY:

18137

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.165

Gnomad4 AMR

AF:

0.293

Gnomad4 ASJ

AF:

0.291

Gnomad4 EAS

AF:

0.0771

Gnomad4 SAS

AF:

0.292

Gnomad4 FIN

AF:

0.303

Gnomad4 NFE

AF:

0.275

Gnomad4 OTH

AF:

0.256

Alfa

AF:

0.254

Hom.:

1388

Bravo

AF:

0.238

Asia WGS

AF:

0.202

AC:

701

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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 50% of patients studied by a panel of primary immunodeficiencies. Number of patients: 48. Only high quality variants are reported. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

7.7

DANN

Benign

0.74

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

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