rs3181052

Positions:

• chr2-113128472-G-A
• chr2-113128472-G-T

Variant summary

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

The NM_173842.3(IL1RN):​c.116+732G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 151,866 control chromosomes in the GnomAD database, including 2,664 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 0.16 (2664 hom., cov: 31)
• Consequence: IL1RN NM_173842.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.28

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL1RN	NM_173842.3	c.116+732G>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.116+732G>A		intron_variant		1	NM_173842.3	ENSP00000387173	P4

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25025 AN: 151748 Hom.: 2667 Cov.: 31

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.582

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.158

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

GnomAD4 genome AF: 0.165 AC: 25026 AN: 151866 Hom.: 2664 Cov.: 31 AF XY: 0.170 AC XY: 12623 AN XY: 74242

Gnomad4 AFR AF: 0.173

Gnomad4 AMR AF: 0.139

Gnomad4 ASJ AF: 0.113

Gnomad4 EAS AF: 0.581

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.247

Gnomad4 NFE AF: 0.128

Gnomad4 OTH AF: 0.156

Alfa AF: 0.132 Hom.: 1309

Bravo AF: 0.162

Asia WGS AF: 0.317 AC: 1100 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.23
DANN	Benign	0.47

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: rs3181052; hg19: chr2-113886049;