rs17486819

Positions:

• chr2-113114229-T-G

Variant summary

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

The XM_011511121.2(IL1RN):​c.-273+1115T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0701 in 152,250 control chromosomes in the GnomAD database, including 469 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 0.070 (469 hom., cov: 32)
• Consequence: IL1RN XM_011511121.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.523

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0786 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1RN	XM_011511121.2	c.-273+1115T>G		intron_variant
IL1RN	XM_047444184.1	c.-273+1115T>G		intron_variant
IL1RN	XM_047444185.1	c.-402+1115T>G		intron_variant
IL1RN	XM_047444186.1	c.-210+1115T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1RN	ENST00000409052.6	c.-273+1115T>G		intron_variant, NMD_transcript_variant		5
IL1RN	ENST00000463073.6	n.302+1115T>G		intron_variant, non_coding_transcript_variant		5
IL1RN	ENST00000465812.6	n.646+1115T>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0701 AC: 10667 AN: 152132 Hom.: 468 Cov.: 32

Gnomad AFR AF: 0.0675

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.0310

Gnomad ASJ AF: 0.0412

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0141

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0804

Gnomad OTH AF: 0.0536

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

GnomAD4 genome AF: 0.0701 AC: 10674 AN: 152250 Hom.: 469 Cov.: 32 AF XY: 0.0698 AC XY: 5199 AN XY: 74442

Gnomad4 AFR AF: 0.0676

Gnomad4 AMR AF: 0.0310

Gnomad4 ASJ AF: 0.0412

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0139

Gnomad4 FIN AF: 0.147

Gnomad4 NFE AF: 0.0803

Gnomad4 OTH AF: 0.0531

Alfa AF: 0.0785 Hom.: 157

Bravo AF: 0.0606

Asia WGS AF: 0.0100 AC: 36 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.0
DANN	Benign	0.82

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17486819; hg19: chr2-113871806;