Variant rs4251986 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_173841.3(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
NM_173841.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.00600

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
IL1RN	NM_173841.3 link	c.11-105G>C	intron_variant	Intron 1 of 5	NP_776213.1	P18510-3
IL1RN	NM_000577.5 link	c.10+1933G>C	intron_variant	Intron 1 of 4	NP_000568.1	P18510-2
IL1RN	NM_001318914.2 link	c.-272-105G>C	intron_variant	Intron 1 of 6	NP_001305843.1	P18510-4A0A024R528

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
IL1RN	ENST00000259206.9 link	c.11-105G>C	intron_variant	Intron 1 of 5	1	ENSP00000259206.5	P18510-3
IL1RN	ENST00000354115.6 link	c.10+1933G>C	intron_variant	Intron 1 of 4	1	ENSP00000329072.3	P18510-2
IL1RN	ENST00000361779.7 link	c.-209-1487G>C	intron_variant	Intron 1 of 5	1	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

Gnomad4 AFR exome

AF:

0.0526

Gnomad4 AMR exome

AF:

0.314

Gnomad4 ASJ exome

AF:

0.289

Gnomad4 EAS exome

AF:

0.0832

Gnomad4 SAS exome

AF:

0.277

Gnomad4 FIN exome

AF:

0.297

Gnomad4 NFE exome

AF:

0.271

Gnomad4 OTH exome

AF:

0.250

GnomAD4 genome

AF:

0.209

AC:

31665

AN:

151854

Hom.:

4065

Cov.:

AF XY:

0.211

AC XY:

15668

AN XY:

74170

show subpopulations

Gnomad4 AFR

AF:

0.0579

Gnomad4 AMR

AF:

0.275

Gnomad4 ASJ

AF:

0.287

Gnomad4 EAS

AF:

0.0983

Gnomad4 SAS

AF:

0.284

Gnomad4 FIN

AF:

0.304

Gnomad4 NFE

AF:

0.269

Gnomad4 OTH

AF:

0.232

Alfa

AF:

0.235

Hom.:

646

Bravo

AF:

0.198

Asia WGS

AF:

0.196

AC:

683

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

May 12, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 43% of patients studied by a panel of primary immunodeficiencies. Number of patients: 38. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.6

DANN

Benign

0.50

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