rs1794065

chr2-113122156-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000259206.9(IL1RN):c.73+2028G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 152,212 control chromosomes in the GnomAD database, including 4,241 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 0.21 (4241 hom., cov: 33)
• Consequence: IL1RN ENST00000259206.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0790

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1RN	NM_000577.5	c.10+4128G>A		intron_variant
IL1RN	NM_001318914.2	c.-39+538G>A		intron_variant
IL1RN	NM_173841.3	c.73+2028G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1RN	ENST00000259206.9	c.73+2028G>A		intron_variant		1
IL1RN	ENST00000354115.6	c.10+4128G>A		intron_variant		1		A1
IL1RN	ENST00000361779.7	c.-39+538G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32172 AN: 152094 Hom.: 4235 Cov.: 33

Gnomad AFR AF: 0.0557

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.0776

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.234

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

GnomAD4 genome AF: 0.211 AC: 32185 AN: 152212 Hom.: 4241 Cov.: 33 AF XY: 0.214 AC XY: 15912 AN XY: 74410

Gnomad4 AFR AF: 0.0556

Gnomad4 AMR AF: 0.283

Gnomad4 ASJ AF: 0.291

Gnomad4 EAS AF: 0.0770

Gnomad4 SAS AF: 0.281

Gnomad4 FIN AF: 0.306

Gnomad4 NFE AF: 0.276

Gnomad4 OTH AF: 0.236

Alfa AF: 0.230 Hom.: 694

Bravo AF: 0.201

Asia WGS AF: 0.188 AC: 655 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	5.8
Dann	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1794065; hg19: chr2-113879733; COSMIC: COSV52080004; COSMIC: COSV52080004;