rs315952

Variant names:

• chr2-113132727-T-C
• rs315952
• NM_173842.3:c.390T>C

Your query was ambiguous. Multiple possible variants found:

• chr2-113132727-T-C
• chr2-113132727-T-A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_173842.3(IL1RN):​c.390T>C​(p.Ser130Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 1,614,016 control chromosomes in the GnomAD database, including 77,305 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.34 (9538 hom., cov: 33)
  • Exomes 𝑓: 0.29 (67767 hom.)
• Consequence: IL1RN NM_173842.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -2.15
• Publications: 136 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: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics, Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 2-113132727-T-C is Benign according to our data. Variant chr2-113132727-T-C is described in ClinVar as Benign. ClinVar VariationId is 330827.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.15 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173842.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RN	NM_173842.3	MANE Select	c.390T>C	p.Ser130Ser	synonymous	Exon 4 of 4	NP_776214.1	P18510-1
	IL1RN	NM_173841.3		c.399T>C	p.Ser133Ser	synonymous	Exon 6 of 6	NP_776213.1	P18510-3
	IL1RN	NM_000577.5		c.336T>C	p.Ser112Ser	synonymous	Exon 5 of 5	NP_000568.1	P18510-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RN	ENST00000409930.4	TSL:1 MANE Select	c.390T>C	p.Ser130Ser	synonymous	Exon 4 of 4	ENSP00000387173.3	P18510-1
	IL1RN	ENST00000259206.9	TSL:1	c.399T>C	p.Ser133Ser	synonymous	Exon 6 of 6	ENSP00000259206.5	P18510-3
	IL1RN	ENST00000354115.6	TSL:1	c.336T>C	p.Ser112Ser	synonymous	Exon 5 of 5	ENSP00000329072.3	P18510-2

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51496 AN: 152098 Hom.: 9523 Cov.: 33

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.588

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.282

GnomAD2 exomes AF: 0.305 AC: 76749 AN: 251324 AF XY: 0.294

Gnomad AFR exome AF: 0.438

Gnomad AMR exome AF: 0.237

Gnomad ASJ exome AF: 0.208

Gnomad EAS exome AF: 0.593

Gnomad FIN exome AF: 0.420

Gnomad NFE exome AF: 0.293

Gnomad OTH exome AF: 0.286

GnomAD4 exome AF: 0.294 AC: 430010 AN: 1461800 Hom.: 67767 Cov.: 37 AF XY: 0.289 AC XY: 210490 AN XY: 727216

African (AFR) AF: 0.438 AC: 14667 AN: 33478

American (AMR) AF: 0.239 AC: 10710 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 5513 AN: 26130

East Asian (EAS) AF: 0.619 AC: 24572 AN: 39700

South Asian (SAS) AF: 0.144 AC: 12445 AN: 86250

European-Finnish (FIN) AF: 0.418 AC: 22326 AN: 53420

Middle Eastern (MID) AF: 0.201 AC: 1160 AN: 5768

European-Non Finnish (NFE) AF: 0.288 AC: 320619 AN: 1111936

Other (OTH) AF: 0.298 AC: 17998 AN: 60394

GnomAD4 genome AF: 0.339 AC: 51534 AN: 152216 Hom.: 9538 Cov.: 33 AF XY: 0.339 AC XY: 25261 AN XY: 74420

African (AFR) AF: 0.433 AC: 17982 AN: 41540

American (AMR) AF: 0.236 AC: 3611 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 720 AN: 3472

East Asian (EAS) AF: 0.588 AC: 3036 AN: 5160

South Asian (SAS) AF: 0.146 AC: 704 AN: 4832

European-Finnish (FIN) AF: 0.417 AC: 4418 AN: 10604

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.296 AC: 20091 AN: 67988

Other (OTH) AF: 0.281 AC: 594 AN: 2114

Alfa AF: 0.303 Hom.: 27947

Bravo AF: 0.334

Asia WGS AF: 0.347 AC: 1206 AN: 3478

EpiCase AF: 0.277

EpiControl AF: 0.274

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Sterile multifocal osteomyelitis with periostitis and pustulosis (3)
-	-	2	not provided (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.16
DANN	Benign	0.45
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs315952; hg19: chr2-113890304; COSMIC: COSV52081886; COSMIC: COSV52081886;