2-113131542-C-T

Variant names:

• chr2-113131542-C-T
• rs4252019
• NM_173842.3:c.318+385C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173842.3(IL1RN):​c.318+385C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 151,906 control chromosomes in the GnomAD database, including 6,211 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.25 (6211 hom., cov: 31)
• Consequence: IL1RN NM_173842.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.68
• Publications: 10 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.567 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+385C>T		intron	N/A	NP_776214.1	P18510-1
	IL1RN	NM_173841.3		c.327+385C>T		intron	N/A	NP_776213.1	P18510-3
	IL1RN	NM_000577.5		c.264+385C>T		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+385C>T		intron	N/A	ENSP00000387173.3	P18510-1
	IL1RN	ENST00000259206.9	TSL:1	c.327+385C>T		intron	N/A	ENSP00000259206.5	P18510-3
	IL1RN	ENST00000354115.6	TSL:1	c.264+385C>T		intron	N/A	ENSP00000329072.3	P18510-2

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37472 AN: 151788 Hom.: 6204 Cov.: 31

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.142

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.585

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.247 AC: 37509 AN: 151906 Hom.: 6211 Cov.: 31 AF XY: 0.251 AC XY: 18621 AN XY: 74210

African (AFR) AF: 0.423 AC: 17492 AN: 41396

American (AMR) AF: 0.168 AC: 2567 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 413 AN: 3470

East Asian (EAS) AF: 0.584 AC: 2992 AN: 5122

South Asian (SAS) AF: 0.108 AC: 518 AN: 4812

European-Finnish (FIN) AF: 0.296 AC: 3116 AN: 10528

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.144 AC: 9791 AN: 67990

Other (OTH) AF: 0.209 AC: 441 AN: 2108

Alfa AF: 0.214 Hom.: 635

Bravo AF: 0.251

Asia WGS AF: 0.327 AC: 1134 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.041
DANN	Benign	0.56
PhyloP100		-2.7
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: rs4252019; hg19: chr2-113889119;