rs452204

Variant names:

• chr2-113131484-G-A
• rs452204
• NM_173842.3:c.318+327G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-113131484-G-A
• chr2-113131484-G-C
• chr2-113131484-G-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_173842.3(IL1RN):​c.318+327G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 151,708 control chromosomes in the GnomAD database, including 15,527 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.45 (15527 hom., cov: 30)
• Consequence: IL1RN NM_173842.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.778
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 2-113131484-G-A is Benign according to our data. Variant chr2-113131484-G-A is described in ClinVar as Benign. ClinVar VariationId is 1232394.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.618 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RN	NM_173842.3	MANE Select	c.318+327G>A		intron	N/A	NP_776214.1
	IL1RN	NM_173841.3		c.327+327G>A		intron	N/A	NP_776213.1
	IL1RN	NM_000577.5		c.264+327G>A		intron	N/A	NP_000568.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RN	ENST00000409930.4	TSL:1 MANE Select	c.318+327G>A		intron	N/A	ENSP00000387173.3
	IL1RN	ENST00000259206.9	TSL:1	c.327+327G>A		intron	N/A	ENSP00000259206.5
	IL1RN	ENST00000354115.6	TSL:1	c.264+327G>A		intron	N/A	ENSP00000329072.3

Frequencies

GnomAD3 genomes AF: 0.448 AC: 67843 AN: 151590 Hom.: 15505 Cov.: 30

Gnomad AFR AF: 0.488

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.397

Gnomad EAS AF: 0.637

Gnomad SAS AF: 0.393

Gnomad FIN AF: 0.552

Gnomad MID AF: 0.385

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.443

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.448 AC: 67907 AN: 151708 Hom.: 15527 Cov.: 30 AF XY: 0.454 AC XY: 33625 AN XY: 74120

African (AFR) AF: 0.488 AC: 20181 AN: 41356

American (AMR) AF: 0.444 AC: 6772 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.397 AC: 1373 AN: 3460

East Asian (EAS) AF: 0.636 AC: 3234 AN: 5086

South Asian (SAS) AF: 0.393 AC: 1894 AN: 4822

European-Finnish (FIN) AF: 0.552 AC: 5796 AN: 10504

Middle Eastern (MID) AF: 0.384 AC: 112 AN: 292

European-Non Finnish (NFE) AF: 0.401 AC: 27254 AN: 67916

Other (OTH) AF: 0.442 AC: 927 AN: 2098

Alfa AF: 0.431 Hom.: 3083

Bravo AF: 0.445

Asia WGS AF: 0.508 AC: 1766 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.7
DANN	Benign	0.63
PhyloP100		0.78
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: rs452204; hg19: chr2-113889061;