rs448341

Variant names:

• chr2-113130888-A-G
• rs448341
• NM_173842.3:c.206-157A>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.206-157A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 152,046 control chromosomes in the GnomAD database, including 4,216 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.22 (4216 hom., cov: 30)
• Consequence: IL1RN NM_173842.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.03
• Publications: 3 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=-0.92).
• BP6: Variant 2-113130888-A-G is Benign according to our data. Variant chr2-113130888-A-G is described in ClinVar as Benign. ClinVar VariationId is 1294768.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.278 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.206-157A>G		intron	N/A	NP_776214.1
	IL1RN	NM_173841.3		c.215-157A>G		intron	N/A	NP_776213.1
	IL1RN	NM_000577.5		c.152-157A>G		intron	N/A	NP_000568.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RN	ENST00000409930.4	TSL:1 MANE Select	c.206-157A>G		intron	N/A	ENSP00000387173.3
	IL1RN	ENST00000259206.9	TSL:1	c.215-157A>G		intron	N/A	ENSP00000259206.5
	IL1RN	ENST00000354115.6	TSL:1	c.152-157A>G		intron	N/A	ENSP00000329072.3

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32695 AN: 151930 Hom.: 4207 Cov.: 30

Gnomad AFR AF: 0.0705

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.0776

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.240

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

GnomAD4 genome AF: 0.215 AC: 32733 AN: 152046 Hom.: 4216 Cov.: 30 AF XY: 0.218 AC XY: 16179 AN XY: 74296

African (AFR) AF: 0.0709 AC: 2942 AN: 41516

American (AMR) AF: 0.284 AC: 4346 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.290 AC: 1005 AN: 3466

East Asian (EAS) AF: 0.0771 AC: 399 AN: 5178

South Asian (SAS) AF: 0.290 AC: 1400 AN: 4822

European-Finnish (FIN) AF: 0.301 AC: 3174 AN: 10540

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

European-Non Finnish (NFE) AF: 0.275 AC: 18675 AN: 67934

Other (OTH) AF: 0.241 AC: 510 AN: 2112

Alfa AF: 0.231 Hom.: 672

Bravo AF: 0.206

Asia WGS AF: 0.198 AC: 688 AN: 3476

ClinVar

ClinVar submissions as Germline

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	-0.92
CADD	Benign	2.1
DANN	Benign	0.51
PhyloP100		-1.0
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: rs448341; hg19: chr2-113888465; COSMIC: COSV52080128; COSMIC: COSV52080128;