2-113132584-G-A

Position:

• chr2-113132584-G-A

Variant summary

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

The NM_173842.3(IL1RN):​c.319-72G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00626 in 1,377,664 control chromosomes in the GnomAD database, including 145 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 0.019 (84 hom., cov: 33)
  • Exomes 𝑓: 0.0046 (61 hom.)
• Consequence: IL1RN NM_173842.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0590

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL1RN	NM_173842.3	c.319-72G>A		intron_variant		ENST00000409930.4	NP_776214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL1RN	ENST00000409930.4	c.319-72G>A		intron_variant		1	NM_173842.3	ENSP00000387173	P4

Frequencies

GnomAD3 genomes AF: 0.0193 AC: 2936 AN: 152230 Hom.: 84 Cov.: 33

Gnomad AFR AF: 0.0607

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.00687

Gnomad ASJ AF: 0.00922

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00310

Gnomad FIN AF: 0.00132

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00307

Gnomad OTH AF: 0.00908

GnomAD4 exome AF: 0.00464 AC: 5688 AN: 1225316 Hom.: 61 AF XY: 0.00434 AC XY: 2697 AN XY: 620946

Gnomad4 AFR exome AF: 0.0579

Gnomad4 AMR exome AF: 0.00398

Gnomad4 ASJ exome AF: 0.00683

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00239

Gnomad4 FIN exome AF: 0.00255

Gnomad4 NFE exome AF: 0.00336

Gnomad4 OTH exome AF: 0.00622

GnomAD4 genome AF: 0.0193 AC: 2939 AN: 152348 Hom.: 84 Cov.: 33 AF XY: 0.0184 AC XY: 1368 AN XY: 74502

Gnomad4 AFR AF: 0.0607

Gnomad4 AMR AF: 0.00673

Gnomad4 ASJ AF: 0.00922

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00311

Gnomad4 FIN AF: 0.00132

Gnomad4 NFE AF: 0.00307

Gnomad4 OTH AF: 0.00899

Alfa AF: 0.0151 Hom.: 9

Bravo AF: 0.0217

Asia WGS AF: 0.00202 AC: 7 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	0.99
DANN	Benign	0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs4252022; hg19: chr2-113890161;