2-113131542-C-T

Position:

• chr2-113131542-C-T

Variant summary

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

The NM_173842.3(IL1RN):​c.318+385C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 151,906 control chromosomes in the GnomAD database, including 6,211 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 0.25 (6211 hom., cov: 31)
• Consequence: IL1RN NM_173842.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.68

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1RN	NM_173842.3	c.318+385C>T		intron_variant		ENST00000409930.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1RN	ENST00000409930.4	c.318+385C>T		intron_variant		1	NM_173842.3	P4

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37472 AN: 151788 Hom.: 6204 Cov.: 31

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.142

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.585

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.247 AC: 37509 AN: 151906 Hom.: 6211 Cov.: 31 AF XY: 0.251 AC XY: 18621 AN XY: 74210

Gnomad4 AFR AF: 0.423

Gnomad4 AMR AF: 0.168

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.584

Gnomad4 SAS AF: 0.108

Gnomad4 FIN AF: 0.296

Gnomad4 NFE AF: 0.144

Gnomad4 OTH AF: 0.209

Alfa AF: 0.214 Hom.: 635

Bravo AF: 0.251

Asia WGS AF: 0.327 AC: 1134 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.041
DANN	Benign	0.56

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: rs4252019; hg19: chr2-113889119;