rs2232354

Positions:

• chr2-113129758-T-G

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.205+94T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 846,010 control chromosomes in the GnomAD database, including 15,930 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (2101 hom., cov: 33)
  • Exomes 𝑓: 0.19 (13829 hom.)
• Consequence: IL1RN NM_173842.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0250

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=-0.82).
• BP6: Variant 2-113129758-T-G is Benign according to our data. Variant chr2-113129758-T-G is described in ClinVar as [Benign]. Clinvar id is 1248659.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1RN	NM_173842.3	c.205+94T>G		intron_variant		ENST00000409930.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1RN	ENST00000409930.4	c.205+94T>G		intron_variant		1	NM_173842.3	P4

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22101 AN: 152112 Hom.: 2099 Cov.: 33

Gnomad AFR AF: 0.0375

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.0397

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.179

GnomAD4 exome AF: 0.190 AC: 131920 AN: 693780 Hom.: 13829 Cov.: 9 AF XY: 0.195 AC XY: 72822 AN XY: 373470

Gnomad4 AFR exome AF: 0.0381

Gnomad4 AMR exome AF: 0.185

Gnomad4 ASJ exome AF: 0.210

Gnomad4 EAS exome AF: 0.0363

Gnomad4 SAS exome AF: 0.245

Gnomad4 FIN exome AF: 0.156

Gnomad4 NFE exome AF: 0.204

Gnomad4 OTH exome AF: 0.185

GnomAD4 genome AF: 0.145 AC: 22111 AN: 152230 Hom.: 2101 Cov.: 33 AF XY: 0.144 AC XY: 10740 AN XY: 74434

Gnomad4 AFR AF: 0.0374

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.215

Gnomad4 EAS AF: 0.0400

Gnomad4 SAS AF: 0.223

Gnomad4 FIN AF: 0.150

Gnomad4 NFE AF: 0.199

Gnomad4 OTH AF: 0.183

Alfa AF: 0.173 Hom.: 644

Bravo AF: 0.143

Asia WGS AF: 0.143 AC: 498 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 29% of patients studied by a panel of primary immunodeficiencies. Number of patients: 28. 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	-0.82
CADD	Benign	2.6
DANN	Benign	0.42

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: rs2232354; hg19: chr2-113887335; COSMIC: COSV52080733;