rs3213448

Positions:

• chr2-113121720-G-A
• chr2-113121720-G-C
• chr2-113121720-G-T

Variant summary

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

The ENST00000259206.9(IL1RN):​c.73+1592G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 605,236 control chromosomes in the GnomAD database, including 7,040 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 0.18 (3184 hom., cov: 32)
  • Exomes 𝑓: 0.12 (3856 hom.)
• Consequence: IL1RN ENST00000259206.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.447

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.562 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1RN	NM_000577.5	c.10+3692G>A		intron_variant
IL1RN	NM_001318914.2	c.-39+102G>A		intron_variant
IL1RN	NM_173841.3	c.73+1592G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1RN	ENST00000259206.9	c.73+1592G>A		intron_variant		1
IL1RN	ENST00000354115.6	c.10+3692G>A		intron_variant		1		A1
IL1RN	ENST00000361779.7	c.-39+102G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27677 AN: 151990 Hom.: 3185 Cov.: 32

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.580

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.156

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.169

GnomAD4 exome AF: 0.123 AC: 55617 AN: 453126 Hom.: 3856 AF XY: 0.122 AC XY: 25956 AN XY: 213494

Gnomad4 AFR exome AF: 0.241

Gnomad4 AMR exome AF: 0.112

Gnomad4 ASJ exome AF: 0.103

Gnomad4 EAS exome AF: 0.574

Gnomad4 SAS exome AF: 0.0957

Gnomad4 FIN exome AF: 0.270

Gnomad4 NFE exome AF: 0.119

Gnomad4 OTH exome AF: 0.138

GnomAD4 genome AF: 0.182 AC: 27687 AN: 152110 Hom.: 3184 Cov.: 32 AF XY: 0.187 AC XY: 13935 AN XY: 74344

Gnomad4 AFR AF: 0.234

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.113

Gnomad4 EAS AF: 0.580

Gnomad4 SAS AF: 0.119

Gnomad4 FIN AF: 0.247

Gnomad4 NFE AF: 0.128

Gnomad4 OTH AF: 0.168

Alfa AF: 0.136 Hom.: 3197

Bravo AF: 0.181

Asia WGS AF: 0.319 AC: 1108 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.64
DANN	Benign	0.25

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3213448; hg19: chr2-113879297;