rs444413

Positions:

• chr2-113128249-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.116+509G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 152,202 control chromosomes in the GnomAD database, including 4,297 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 0.22 (4297 hom., cov: 32)
• Consequence: IL1RN NM_173842.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05

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 (AMR) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1RN	NM_173842.3	c.116+509G>A		intron_variant		ENST00000409930.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1RN	ENST00000409930.4	c.116+509G>A		intron_variant		1	NM_173842.3	P4

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32898 AN: 152082 Hom.: 4289 Cov.: 32

Gnomad AFR AF: 0.0728

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.0773

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.239

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

GnomAD4 genome AF: 0.216 AC: 32935 AN: 152202 Hom.: 4297 Cov.: 32 AF XY: 0.219 AC XY: 16289 AN XY: 74398

Gnomad4 AFR AF: 0.0732

Gnomad4 AMR AF: 0.283

Gnomad4 ASJ AF: 0.291

Gnomad4 EAS AF: 0.0767

Gnomad4 SAS AF: 0.281

Gnomad4 FIN AF: 0.306

Gnomad4 NFE AF: 0.276

Gnomad4 OTH AF: 0.241

Alfa AF: 0.239 Hom.: 921

Bravo AF: 0.207

Asia WGS AF: 0.192 AC: 669 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	0.56
DANN	Benign	0.60

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: rs444413; hg19: chr2-113885826; COSMIC: COSV52080015;