rs2234678

Variant names:

• chr2-113117988-A-G
• rs2234678
• ENST00000259206.9:c.-31A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000486167.1(IL1RN):​n.8A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 1,357,394 control chromosomes in the GnomAD database, including 43,389 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (4081 hom., cov: 33)
  • Exomes 𝑓: 0.25 (39308 hom.)
• Consequence: IL1RN ENST00000486167.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.25
• Publications: 21 publications found

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]

IL1RN Gene-Disease associations (from GenCC):

• sterile multifocal osteomyelitis with periostitis and pustulosis

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 2-113117988-A-G is Benign according to our data. Variant chr2-113117988-A-G is described in ClinVar as Benign. ClinVar VariationId is 330820.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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000486167.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RN	NM_173841.3		c.-31A>G		5_prime_UTR	Exon 1 of 6	NP_776213.1
	IL1RN	NM_000577.5		c.-31A>G		5_prime_UTR	Exon 1 of 5	NP_000568.1
	IL1RN	NM_001318914.2		c.-313A>G		5_prime_UTR	Exon 1 of 7	NP_001305843.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RN	ENST00000259206.9	TSL:1	c.-31A>G		5_prime_UTR	Exon 1 of 6	ENSP00000259206.5
	IL1RN	ENST00000354115.6	TSL:1	c.-31A>G		5_prime_UTR	Exon 1 of 5	ENSP00000329072.3
	IL1RN	ENST00000361779.7	TSL:1	c.-250A>G		5_prime_UTR	Exon 1 of 6	ENSP00000354816.3

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31808 AN: 152080 Hom.: 4074 Cov.: 33

Gnomad AFR AF: 0.0582

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.0973

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.230

GnomAD2 exomes AF: 0.253 AC: 63655 AN: 251438 AF XY: 0.256

Gnomad AFR exome AF: 0.0510

Gnomad AMR exome AF: 0.321

Gnomad ASJ exome AF: 0.300

Gnomad EAS exome AF: 0.0923

Gnomad FIN exome AF: 0.304

Gnomad NFE exome AF: 0.265

Gnomad OTH exome AF: 0.265

GnomAD4 exome AF: 0.248 AC: 299099 AN: 1205194 Hom.: 39308 Cov.: 17 AF XY: 0.249 AC XY: 152795 AN XY: 612620

African (AFR) AF: 0.0465 AC: 1353 AN: 29102

American (AMR) AF: 0.315 AC: 13991 AN: 44386

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 7024 AN: 24494

East Asian (EAS) AF: 0.0828 AC: 3195 AN: 38602

South Asian (SAS) AF: 0.273 AC: 22113 AN: 81086

European-Finnish (FIN) AF: 0.296 AC: 15735 AN: 53168

Middle Eastern (MID) AF: 0.210 AC: 1112 AN: 5286

European-Non Finnish (NFE) AF: 0.253 AC: 222104 AN: 877310

Other (OTH) AF: 0.241 AC: 12472 AN: 51760

GnomAD4 genome AF: 0.209 AC: 31825 AN: 152200 Hom.: 4081 Cov.: 33 AF XY: 0.212 AC XY: 15779 AN XY: 74394

African (AFR) AF: 0.0581 AC: 2415 AN: 41570

American (AMR) AF: 0.278 AC: 4253 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 1019 AN: 3470

East Asian (EAS) AF: 0.0968 AC: 502 AN: 5188

South Asian (SAS) AF: 0.283 AC: 1365 AN: 4818

European-Finnish (FIN) AF: 0.304 AC: 3215 AN: 10568

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.269 AC: 18281 AN: 67972

Other (OTH) AF: 0.232 AC: 489 AN: 2112

Alfa AF: 0.251 Hom.: 5893

Bravo AF: 0.199

Asia WGS AF: 0.195 AC: 679 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)
-	-	1	Sterile multifocal osteomyelitis with periostitis and pustulosis (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.39
DANN	Benign	0.71
PhyloP100		-1.3
PromoterAI		0.099	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2234678; hg19: chr2-113875565; COSMIC: COSV52080796; COSMIC: COSV52080796;