2-113119961-G-C

Position:

• chr2-113119961-G-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.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 ENST00000259206.9 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.00600

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=-0.87).
• 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	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL1RN	NM_000577.5	c.10+1933G>C		intron_variant			NP_000568.1
IL1RN	NM_001318914.2	c.-272-105G>C		intron_variant			NP_001305843.1
IL1RN	NM_173841.3	c.11-105G>C		intron_variant			NP_776213.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL1RN	ENST00000259206.9	c.11-105G>C		intron_variant		1		ENSP00000259206
IL1RN	ENST00000354115.6	c.10+1933G>C		intron_variant		1		ENSP00000329072	A1
IL1RN	ENST00000361779.7	c.-209-1487G>C		intron_variant		1		ENSP00000354816

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31650 AN: 151734 Hom.: 4059 Cov.: 30

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

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.: 30 AF XY: 0.211 AC XY: 15668 AN XY: 74170

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

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 12, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

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

Other links and lift over

dbSNP: rs4251986; hg19: chr2-113877538; COSMIC: COSV52080812; COSMIC: COSV52080812;