rs315931

Positions:

• chr2-113112266-C-A

Variant summary

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

The XM_011511121.2(IL1RN):​c.-387-734C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.604 in 152,100 control chromosomes in the GnomAD database, including 28,492 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 0.60 (28492 hom., cov: 33)
• Consequence: IL1RN XM_011511121.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.435

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 (NFE) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL1RN	XM_011511121.2	c.-387-734C>A		intron_variant			XP_011509423.1
IL1RN	XM_047444184.1	c.-387-734C>A		intron_variant			XP_047300140.1
IL1RN	XM_047444185.1	c.-516-734C>A		intron_variant			XP_047300141.1
IL1RN	XM_047444186.1	c.-324-734C>A		intron_variant			XP_047300142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL1RN	ENST00000409052.6	c.-387-734C>A		intron_variant, NMD_transcript_variant		5		ENSP00000387210
IL1RN	ENST00000463073.6	n.188-734C>A		intron_variant, non_coding_transcript_variant		5
IL1RN	ENST00000465812.6	n.532-734C>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.604 AC: 91790 AN: 151982 Hom.: 28500 Cov.: 33

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.773

Gnomad AMR AF: 0.587

Gnomad ASJ AF: 0.654

Gnomad EAS AF: 0.372

Gnomad SAS AF: 0.544

Gnomad FIN AF: 0.611

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.695

Gnomad OTH AF: 0.604

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

GnomAD4 genome AF: 0.604 AC: 91810 AN: 152100 Hom.: 28492 Cov.: 33 AF XY: 0.598 AC XY: 44444 AN XY: 74376

Gnomad4 AFR AF: 0.486

Gnomad4 AMR AF: 0.585

Gnomad4 ASJ AF: 0.654

Gnomad4 EAS AF: 0.373

Gnomad4 SAS AF: 0.545

Gnomad4 FIN AF: 0.611

Gnomad4 NFE AF: 0.695

Gnomad4 OTH AF: 0.605

Alfa AF: 0.674 Hom.: 57761

Bravo AF: 0.596

Asia WGS AF: 0.482 AC: 1678 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	0.70
DANN	Benign	0.78

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs315931; hg19: chr2-113869843;