2-113118054-T-C

Variant summary

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

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.703

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=-0.88).
• 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	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1RN	NM_000577.5	c.10+26T>C		intron_variant
IL1RN	NM_001318914.2	c.-273+26T>C		intron_variant
IL1RN	NM_173841.3	c.10+26T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1RN	ENST00000259206.9	c.10+26T>C		intron_variant		1
IL1RN	ENST00000354115.6	c.10+26T>C		intron_variant		1		A1
IL1RN	ENST00000361779.7	c.-210+26T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31842 AN: 152112 Hom.: 4091 Cov.: 33

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

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.: 30 AF XY: 0.261 AC XY: 189326 AN XY: 724622

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.: 33 AF XY: 0.212 AC XY: 15801 AN XY: 74422

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: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 49% of patients studied by a panel of primary immunodeficiencies. Number of patients: 47. 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	-0.88
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

Other links and lift over

dbSNP: rs16065; hg19: chr2-113875631; COSMIC: COSV52079930; COSMIC: COSV52079930;