rs452204

Positions:

• chr2-113131484-G-A
• chr2-113131484-G-C
• chr2-113131484-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_173842.3(IL1RN):​c.318+327G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 151,708 control chromosomes in the GnomAD database, including 15,527 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.45 (15527 hom., cov: 30)
• Consequence: IL1RN NM_173842.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.778

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 2-113131484-G-A is Benign according to our data. Variant chr2-113131484-G-A is described in ClinVar as [Benign]. Clinvar id is 1232394.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1RN	NM_173842.3	c.318+327G>A		intron_variant		ENST00000409930.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1RN	ENST00000409930.4	c.318+327G>A		intron_variant		1	NM_173842.3	P4

Frequencies

GnomAD3 genomes AF: 0.448 AC: 67843 AN: 151590 Hom.: 15505 Cov.: 30

Gnomad AFR AF: 0.488

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.397

Gnomad EAS AF: 0.637

Gnomad SAS AF: 0.393

Gnomad FIN AF: 0.552

Gnomad MID AF: 0.385

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.443

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

GnomAD4 genome AF: 0.448 AC: 67907 AN: 151708 Hom.: 15527 Cov.: 30 AF XY: 0.454 AC XY: 33625 AN XY: 74120

Gnomad4 AFR AF: 0.488

Gnomad4 AMR AF: 0.444

Gnomad4 ASJ AF: 0.397

Gnomad4 EAS AF: 0.636

Gnomad4 SAS AF: 0.393

Gnomad4 FIN AF: 0.552

Gnomad4 NFE AF: 0.401

Gnomad4 OTH AF: 0.442

Alfa AF: 0.431 Hom.: 3083

Bravo AF: 0.445

Asia WGS AF: 0.508 AC: 1766 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.7
DANN	Benign	0.63

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: rs452204; hg19: chr2-113889061;