rs315920

Positions:

• chr2-113115441-C-T

Variant summary

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

The XM_011511121.2(IL1RN):​c.-273+2327C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 152,166 control chromosomes in the GnomAD database, including 2,030 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 (2030 hom., cov: 31)
  • Exomes 𝑓: 0.071 (0 hom.)
• Consequence: IL1RN XM_011511121.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.02

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1RN	XM_011511121.2	c.-273+2327C>T		intron_variant
IL1RN	XM_047444184.1	c.-273+2327C>T		intron_variant
IL1RN	XM_047444185.1	c.-401-2096C>T		intron_variant
IL1RN	XM_047444186.1	c.-210+2327C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1RN	ENST00000409052.6	c.-273+2327C>T		intron_variant, NMD_transcript_variant		5
IL1RN	ENST00000463073.6	n.303-64C>T		intron_variant, non_coding_transcript_variant		5
IL1RN	ENST00000465812.6	n.647-2096C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23055 AN: 151950 Hom.: 2030 Cov.: 31

Gnomad AFR AF: 0.0928

Gnomad AMI AF: 0.153

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.0218

Gnomad SAS AF: 0.0443

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.141

GnomAD4 exome AF: 0.0714 AC: 7 AN: 98 Hom.: 0 AF XY: 0.0735 AC XY: 5 AN XY: 68

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.125

Gnomad4 NFE exome AF: 0.0714

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.152 AC: 23053 AN: 152068 Hom.: 2030 Cov.: 31 AF XY: 0.147 AC XY: 10919 AN XY: 74348

Gnomad4 AFR AF: 0.0927

Gnomad4 AMR AF: 0.116

Gnomad4 ASJ AF: 0.187

Gnomad4 EAS AF: 0.0221

Gnomad4 SAS AF: 0.0439

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.140

Alfa AF: 0.198 Hom.: 3112

Bravo AF: 0.146

Asia WGS AF: 0.0290 AC: 105 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.79
DANN	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs315920; hg19: chr2-113873018;