rs17207494

Positions:

• chr2-113106433-A-C

Variant summary

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

The XM_011511121.2(IL1RN):​c.-471-4683A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 152,146 control chromosomes in the GnomAD database, including 8,356 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 0.32 (8356 hom., cov: 33)
• Consequence: IL1RN XM_011511121.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.343

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1RN	XM_011511121.2	c.-471-4683A>C		intron_variant
IL1RN	XM_047444184.1	c.-643-781A>C		intron_variant
IL1RN	XM_047444185.1	c.-600-4683A>C		intron_variant
IL1RN	XM_047444186.1	c.-408-4683A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1RN	ENST00000409052.6	c.-471-4683A>C		intron_variant, NMD_transcript_variant		5
IL1RN	ENST00000463073.6	n.104-4683A>C		intron_variant, non_coding_transcript_variant		5
IL1RN	ENST00000465812.6	n.276-781A>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48467 AN: 152028 Hom.: 8350 Cov.: 33

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.531

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.0673

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.352

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

GnomAD4 genome AF: 0.319 AC: 48491 AN: 152146 Hom.: 8356 Cov.: 33 AF XY: 0.314 AC XY: 23310 AN XY: 74354

Gnomad4 AFR AF: 0.232

Gnomad4 AMR AF: 0.321

Gnomad4 ASJ AF: 0.389

Gnomad4 EAS AF: 0.0672

Gnomad4 SAS AF: 0.347

Gnomad4 FIN AF: 0.299

Gnomad4 NFE AF: 0.383

Gnomad4 OTH AF: 0.355

Alfa AF: 0.334 Hom.: 1113

Bravo AF: 0.318

Asia WGS AF: 0.257 AC: 892 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.61
DANN	Benign	0.67

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17207494; hg19: chr2-113864010;