rs17042888

chr2-113104596-G-Achr2-113104596-G-Cchr2-113104596-G-T

Variant summary

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

The XM_011511121.2(IL1RN):c.-472+5007G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,166 control chromosomes in the GnomAD database, including 1,278 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 0.12 (1278 hom., cov: 32)
• Consequence: IL1RN XM_011511121.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.194

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1RN	XM_011511121.2	c.-472+5007G>A		intron_variant
IL1RN	XM_047444184.1	c.-643-2618G>A		intron_variant
IL1RN	XM_047444185.1	c.-601+5007G>A		intron_variant
IL1RN	XM_047444186.1	c.-409+5007G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1RN	ENST00000409052.6	c.-472+5007G>A		intron_variant, NMD_transcript_variant		5
IL1RN	ENST00000463073.6	n.103+5007G>A		intron_variant, non_coding_transcript_variant		5
IL1RN	ENST00000465812.6	n.276-2618G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18070 AN: 152048 Hom.: 1282 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.0562

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0828

Gnomad OTH AF: 0.0887

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

GnomAD4 genome AF: 0.119 AC: 18065 AN: 152166 Hom.: 1278 Cov.: 32 AF XY: 0.122 AC XY: 9104 AN XY: 74424

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.0562

Gnomad4 EAS AF: 0.280

Gnomad4 SAS AF: 0.108

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.0828

Gnomad4 OTH AF: 0.0887

Alfa AF: 0.0835 Hom.: 978

Bravo AF: 0.120

Asia WGS AF: 0.173 AC: 603 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	5.1
Dann	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17042888; hg19: chr2-113862173;