rs454078

chr2-113131216-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_173842.3(IL1RN):c.318+59A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 1,034,722 control chromosomes in the GnomAD database, including 35,094 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (4274 hom., cov: 30)
  • Exomes 𝑓: 0.25 (30820 hom.)
• Consequence: IL1RN NM_173842.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.532

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 2-113131216-A-T is Benign according to our data. Variant chr2-113131216-A-T is described in ClinVar as [Benign]. Clinvar id is 1260921.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1RN	NM_173842.3	c.318+59A>T		intron_variant		ENST00000409930.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1RN	ENST00000409930.4	c.318+59A>T		intron_variant		1	NM_173842.3	P4

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32743 AN: 151872 Hom.: 4264 Cov.: 30

Gnomad AFR AF: 0.0694

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.0780

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.238

GnomAD4 exome AF: 0.253 AC: 223473 AN: 882732 Hom.: 30820 AF XY: 0.254 AC XY: 117533 AN XY: 462502

Gnomad4 AFR exome AF: 0.0628

Gnomad4 AMR exome AF: 0.322

Gnomad4 ASJ exome AF: 0.289

Gnomad4 EAS exome AF: 0.0585

Gnomad4 SAS exome AF: 0.276

Gnomad4 FIN exome AF: 0.298

Gnomad4 NFE exome AF: 0.260

Gnomad4 OTH exome AF: 0.247

GnomAD4 genome AF: 0.216 AC: 32782 AN: 151990 Hom.: 4274 Cov.: 30 AF XY: 0.219 AC XY: 16254 AN XY: 74290

Gnomad4 AFR AF: 0.0698

Gnomad4 AMR AF: 0.286

Gnomad4 ASJ AF: 0.291

Gnomad4 EAS AF: 0.0774

Gnomad4 SAS AF: 0.286

Gnomad4 FIN AF: 0.305

Gnomad4 NFE AF: 0.275

Gnomad4 OTH AF: 0.240

Alfa AF: 0.240 Hom.: 674

Bravo AF: 0.206

Asia WGS AF: 0.197 AC: 687 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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 46% of patients studied by a panel of primary immunodeficiencies. Number of patients: 44. 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	-0.92
Cadd	Benign	0.092
Dann	Benign	0.69

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

Other links and lift over

dbSNP: rs454078; hg19: chr2-113888793; COSMIC: COSV52080160; COSMIC: COSV52080160;