2-113126129-T-C

Variant names:

• chr2-113126129-T-C
• rs315934
• ENST00000259206.9:c.74-1560T>C

Variant summary

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

The ENST00000259206.9(IL1RN):​c.74-1560T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 152,222 control chromosomes in the GnomAD database, including 1,900 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 0.15 (1900 hom., cov: 32)
• Consequence: IL1RN ENST00000259206.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.199
• Publications: 11 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1RN	NM_173841.3	c.74-1560T>C		intron_variant	Intron 2 of 5		NP_776213.1
IL1RN	NM_000577.5	c.11-1560T>C		intron_variant	Intron 1 of 4		NP_000568.1
IL1RN	NM_001318914.2	c.-38-1560T>C		intron_variant	Intron 3 of 6		NP_001305843.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1RN	ENST00000259206.9	c.74-1560T>C		intron_variant	Intron 2 of 5	1		ENSP00000259206.5
IL1RN	ENST00000354115.6	c.11-1560T>C		intron_variant	Intron 1 of 4	1		ENSP00000329072.3
IL1RN	ENST00000361779.7	c.-38-1560T>C		intron_variant	Intron 2 of 5	1		ENSP00000354816.3

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22379 AN: 152104 Hom.: 1899 Cov.: 32

Gnomad AFR AF: 0.0919

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.0233

Gnomad SAS AF: 0.0444

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.139

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

GnomAD4 genome AF: 0.147 AC: 22380 AN: 152222 Hom.: 1900 Cov.: 32 AF XY: 0.142 AC XY: 10598 AN XY: 74416

African (AFR) AF: 0.0918 AC: 3815 AN: 41548

American (AMR) AF: 0.106 AC: 1628 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 628 AN: 3470

East Asian (EAS) AF: 0.0236 AC: 122 AN: 5178

South Asian (SAS) AF: 0.0442 AC: 213 AN: 4820

European-Finnish (FIN) AF: 0.155 AC: 1640 AN: 10584

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.204 AC: 13879 AN: 68004

Other (OTH) AF: 0.137 AC: 290 AN: 2114

Alfa AF: 0.194 Hom.: 1377

Bravo AF: 0.141

Asia WGS AF: 0.0290 AC: 103 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.75
DANN	Benign	0.60
PhyloP100		-0.20
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: rs315934; hg19: chr2-113883706;