rs2234676

Positions:

• chr2-113117851-G-A

Variant summary

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

The XM_011511121.2(IL1RN):​c.-272-2215G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 706,342 control chromosomes in the GnomAD database, including 22,450 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (4092 hom., cov: 32)
  • Exomes 𝑓: 0.25 (18358 hom.)
• Consequence: IL1RN XM_011511121.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.968

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 2-113117851-G-A is Benign according to our data. Variant chr2-113117851-G-A is described in ClinVar as [Benign]. Clinvar id is 1294755.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL1RN	XM_011511121.2	c.-272-2215G>A		intron_variant			XP_011509423.1
IL1RN	XM_047444184.1	c.-272-2215G>A		intron_variant			XP_047300140.1
IL1RN	XM_047444185.1	c.-273+186G>A		intron_variant			XP_047300141.1
IL1RN	XM_047444186.1	c.-209-3597G>A		intron_variant			XP_047300142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL1RN	ENST00000409052.6	c.-272-2215G>A		intron_variant, NMD_transcript_variant		5		ENSP00000387210
IL1RN	ENST00000465812.6	n.775+186G>A		intron_variant, non_coding_transcript_variant		5
IL1RN	ENST00000259206.9			upstream_gene_variant		1		ENSP00000259206

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31821 AN: 152036 Hom.: 4086 Cov.: 32

Gnomad AFR AF: 0.0583

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.0971

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.217

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.231

GnomAD4 exome AF: 0.247 AC: 137057 AN: 554188 Hom.: 18358 Cov.: 3 AF XY: 0.248 AC XY: 74147 AN XY: 299140

Gnomad4 AFR exome AF: 0.0536

Gnomad4 AMR exome AF: 0.301

Gnomad4 ASJ exome AF: 0.281

Gnomad4 EAS exome AF: 0.0820

Gnomad4 SAS exome AF: 0.265

Gnomad4 FIN exome AF: 0.286

Gnomad4 NFE exome AF: 0.260

Gnomad4 OTH exome AF: 0.246

GnomAD4 genome AF: 0.209 AC: 31836 AN: 152154 Hom.: 4092 Cov.: 32 AF XY: 0.212 AC XY: 15798 AN XY: 74396

Gnomad4 AFR AF: 0.0581

Gnomad4 AMR AF: 0.278

Gnomad4 ASJ AF: 0.293

Gnomad4 EAS AF: 0.0966

Gnomad4 SAS AF: 0.284

Gnomad4 FIN AF: 0.305

Gnomad4 NFE AF: 0.269

Gnomad4 OTH AF: 0.233

Alfa AF: 0.232 Hom.: 587

Bravo AF: 0.199

Asia WGS AF: 0.195 AC: 678 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-0.87
CADD	Benign	2.2
DANN	Benign	0.31

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2234676; hg19: chr2-113875428; COSMIC: COSV52079910; COSMIC: COSV52079910;