chr2-113117504-C-T

Position:

• chr2-113117504-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.-272-2562C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 164,572 control chromosomes in the GnomAD database, including 4,349 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 (4098 hom., cov: 33)
  • Exomes 𝑓: 0.18 (251 hom.)
• Consequence: IL1RN XM_011511121.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL1RN	XM_011511121.2	c.-272-2562C>T		intron_variant			XP_011509423.1
IL1RN	XM_047444184.1	c.-272-2562C>T		intron_variant			XP_047300140.1
IL1RN	XM_047444185.1	c.-401-33C>T		intron_variant			XP_047300141.1
IL1RN	XM_047444186.1	c.-209-3944C>T		intron_variant			XP_047300142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL1RN	ENST00000409052.6	n.-272-2562C>T		intron_variant		5		ENSP00000387210.1
IL1RN	ENST00000465812.6	n.647-33C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31844 AN: 152102 Hom.: 4092 Cov.: 33

Gnomad AFR AF: 0.0584

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.0970

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.231

GnomAD4 exome AF: 0.178 AC: 2200 AN: 12352 Hom.: 251 Cov.: 0 AF XY: 0.181 AC XY: 1167 AN XY: 6440

Gnomad4 AFR exome AF: 0.0452

Gnomad4 AMR exome AF: 0.248

Gnomad4 ASJ exome AF: 0.129

Gnomad4 EAS exome AF: 0.0296

Gnomad4 SAS exome AF: 0.191

Gnomad4 FIN exome AF: 0.120

Gnomad4 NFE exome AF: 0.181

Gnomad4 OTH exome AF: 0.149

GnomAD4 genome AF: 0.209 AC: 31859 AN: 152220 Hom.: 4098 Cov.: 33 AF XY: 0.212 AC XY: 15804 AN XY: 74426

Gnomad4 AFR AF: 0.0582

Gnomad4 AMR AF: 0.278

Gnomad4 ASJ AF: 0.293

Gnomad4 EAS AF: 0.0965

Gnomad4 SAS AF: 0.284

Gnomad4 FIN AF: 0.305

Gnomad4 NFE AF: 0.269

Gnomad4 OTH AF: 0.232

Alfa AF: 0.215 Hom.: 1230

Bravo AF: 0.199

Asia WGS AF: 0.196 AC: 681 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	0.39
DANN	Benign	0.33

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11677397; hg19: chr2-113875081; COSMIC: COSV52079904; COSMIC: COSV52079904;