rs315951

Variant names:

• chr2-113133009-C-G
• rs315951
• NM_173842.3:c.*138C>G

Variant summary

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

The NM_173842.3(IL1RN):​c.*138C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 787,330 control chromosomes in the GnomAD database, including 42,486 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.34 (9445 hom., cov: 33)
  • Exomes 𝑓: 0.30 (33041 hom.)
• Consequence: IL1RN NM_173842.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.610
• Publications: 52 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 2-113133009-C-G is Benign according to our data. Variant chr2-113133009-C-G is described in ClinVar as Benign. ClinVar VariationId is 330832.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.59 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.*138C>G		3_prime_UTR	Exon 4 of 4	NP_776214.1	P18510-1
	IL1RN	NM_173841.3		c.*138C>G		3_prime_UTR	Exon 6 of 6	NP_776213.1	P18510-3
	IL1RN	NM_000577.5		c.*138C>G		3_prime_UTR	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.*138C>G		3_prime_UTR	Exon 4 of 4	ENSP00000387173.3	P18510-1
	IL1RN	ENST00000259206.9	TSL:1	c.*138C>G		3_prime_UTR	Exon 6 of 6	ENSP00000259206.5	P18510-3
	IL1RN	ENST00000354115.6	TSL:1	c.*138C>G		3_prime_UTR	Exon 5 of 5	ENSP00000329072.3	P18510-2

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51270 AN: 152048 Hom.: 9431 Cov.: 33

Gnomad AFR AF: 0.424

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.608

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.282

GnomAD4 exome AF: 0.304 AC: 193077 AN: 635164 Hom.: 33041 Cov.: 8 AF XY: 0.295 AC XY: 100465 AN XY: 340110

African (AFR) AF: 0.426 AC: 7288 AN: 17116

American (AMR) AF: 0.239 AC: 8368 AN: 35034

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 4230 AN: 20276

East Asian (EAS) AF: 0.644 AC: 21027 AN: 32670

South Asian (SAS) AF: 0.145 AC: 9435 AN: 65018

European-Finnish (FIN) AF: 0.419 AC: 18184 AN: 43356

Middle Eastern (MID) AF: 0.206 AC: 569 AN: 2764

European-Non Finnish (NFE) AF: 0.295 AC: 113977 AN: 385926

Other (OTH) AF: 0.303 AC: 9999 AN: 33004

GnomAD4 genome AF: 0.337 AC: 51306 AN: 152166 Hom.: 9445 Cov.: 33 AF XY: 0.338 AC XY: 25155 AN XY: 74392

African (AFR) AF: 0.424 AC: 17603 AN: 41524

American (AMR) AF: 0.235 AC: 3600 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 714 AN: 3472

East Asian (EAS) AF: 0.607 AC: 3136 AN: 5164

South Asian (SAS) AF: 0.145 AC: 698 AN: 4822

European-Finnish (FIN) AF: 0.417 AC: 4413 AN: 10592

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.297 AC: 20174 AN: 67984

Other (OTH) AF: 0.281 AC: 592 AN: 2108

Alfa AF: 0.331 Hom.: 1285

Bravo AF: 0.332

Asia WGS AF: 0.355 AC: 1234 AN: 3478

ClinVar

ClinVar submissions

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	-0.92
CADD	Benign	7.0
DANN	Benign	0.51
PhyloP100		0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs315951; hg19: chr2-113890586;