rs380092

Variant names:

• chr2-113131323-T-A
• rs380092
• NM_173842.3:c.318+166T>A

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.318+166T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 152,062 control chromosomes in the GnomAD database, including 27,520 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.58 (27520 hom., cov: 32)
• Consequence: IL1RN NM_173842.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0900
• Publications: 34 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=-0.85).
• BP6: Variant 2-113131323-T-A is Benign according to our data. Variant chr2-113131323-T-A is described in ClinVar as Benign. ClinVar VariationId is 1251642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.818 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.318+166T>A		intron	N/A	NP_776214.1	P18510-1
	IL1RN	NM_173841.3		c.327+166T>A		intron	N/A	NP_776213.1	P18510-3
	IL1RN	NM_000577.5		c.264+166T>A		intron	N/A	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.318+166T>A		intron	N/A	ENSP00000387173.3	P18510-1
	IL1RN	ENST00000259206.9	TSL:1	c.327+166T>A		intron	N/A	ENSP00000259206.5	P18510-3
	IL1RN	ENST00000354115.6	TSL:1	c.264+166T>A		intron	N/A	ENSP00000329072.3	P18510-2

Frequencies

GnomAD3 genomes AF: 0.575 AC: 87410 AN: 151944 Hom.: 27498 Cov.: 32

Gnomad AFR AF: 0.321

Gnomad AMI AF: 0.696

Gnomad AMR AF: 0.708

Gnomad ASJ AF: 0.758

Gnomad EAS AF: 0.396

Gnomad SAS AF: 0.838

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.710

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.636

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

GnomAD4 genome AF: 0.575 AC: 87476 AN: 152062 Hom.: 27520 Cov.: 32 AF XY: 0.578 AC XY: 42961 AN XY: 74338

African (AFR) AF: 0.322 AC: 13334 AN: 41470

American (AMR) AF: 0.708 AC: 10825 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.758 AC: 2628 AN: 3466

East Asian (EAS) AF: 0.397 AC: 2050 AN: 5164

South Asian (SAS) AF: 0.839 AC: 4049 AN: 4824

European-Finnish (FIN) AF: 0.606 AC: 6393 AN: 10558

Middle Eastern (MID) AF: 0.719 AC: 210 AN: 292

European-Non Finnish (NFE) AF: 0.677 AC: 46000 AN: 67974

Other (OTH) AF: 0.640 AC: 1352 AN: 2114

Alfa AF: 0.598 Hom.: 3527

Bravo AF: 0.567

Asia WGS AF: 0.634 AC: 2202 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.3
DANN	Benign	0.43
PhyloP100		-0.090
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: rs380092; hg19: chr2-113888900;