2-113118636-T-G

Variant names:

• chr2-113118636-T-G
• rs315919
• ENST00000259206.9:c.10+608T>G

Variant summary

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

The NM_173841.3(IL1RN):​c.10+608T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 152,124 control chromosomes in the GnomAD database, including 23,487 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 0.55 (23487 hom., cov: 33)
• Consequence: IL1RN NM_173841.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.187
• Publications: 16 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173841.3. 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_173841.3		c.10+608T>G		intron	N/A	NP_776213.1	P18510-3
	IL1RN	NM_000577.5		c.10+608T>G		intron	N/A	NP_000568.1	P18510-2
	IL1RN	NM_001318914.2		c.-273+608T>G		intron	N/A	NP_001305843.1	P18510-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RN	ENST00000259206.9	TSL:1	c.10+608T>G		intron	N/A	ENSP00000259206.5	P18510-3
	IL1RN	ENST00000354115.6	TSL:1	c.10+608T>G		intron	N/A	ENSP00000329072.3	P18510-2
	IL1RN	ENST00000361779.7	TSL:1	c.-210+608T>G		intron	N/A	ENSP00000354816.3	P18510-4

Frequencies

GnomAD3 genomes AF: 0.553 AC: 84104 AN: 152006 Hom.: 23476 Cov.: 33

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.602

Gnomad AMR AF: 0.557

Gnomad ASJ AF: 0.597

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.605

Gnomad NFE AF: 0.603

Gnomad OTH AF: 0.562

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

GnomAD4 genome AF: 0.553 AC: 84162 AN: 152124 Hom.: 23487 Cov.: 33 AF XY: 0.547 AC XY: 40660 AN XY: 74388

African (AFR) AF: 0.510 AC: 21156 AN: 41482

American (AMR) AF: 0.556 AC: 8497 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.597 AC: 2072 AN: 3472

East Asian (EAS) AF: 0.412 AC: 2133 AN: 5180

South Asian (SAS) AF: 0.556 AC: 2684 AN: 4830

European-Finnish (FIN) AF: 0.447 AC: 4721 AN: 10566

Middle Eastern (MID) AF: 0.606 AC: 177 AN: 292

European-Non Finnish (NFE) AF: 0.603 AC: 40985 AN: 67990

Other (OTH) AF: 0.562 AC: 1189 AN: 2114

Alfa AF: 0.589 Hom.: 71677

Bravo AF: 0.558

Asia WGS AF: 0.486 AC: 1690 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.3
DANN	Benign	0.63
PhyloP100		-0.19
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs315919; hg19: chr2-113876213;