chr2-113129881-G-T

Variant names:

• chr2-113129881-G-T
• rs408392
• ENST00000472292.1:n.471G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000472292.1(IL1RN):​n.471G>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 550,424 control chromosomes in the GnomAD database, including 17,409 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (4284 hom., cov: 32)
  • Exomes 𝑓: 0.25 (13125 hom.)
• Consequence: IL1RN ENST00000472292.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.479
• Publications: 14 publications found

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]

IL1RN Gene-Disease associations (from GenCC):

• sterile multifocal osteomyelitis with periostitis and pustulosis

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 2-113129881-G-T is Benign according to our data. Variant chr2-113129881-G-T is described in ClinVar as Benign. ClinVar VariationId is 1259882.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1RN	NM_173842.3	c.205+217G>T		intron_variant	Intron 2 of 3	ENST00000409930.4	NP_776214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1RN	ENST00000409930.4	c.205+217G>T		intron_variant	Intron 2 of 3	1	NM_173842.3	ENSP00000387173.3

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32818 AN: 152000 Hom.: 4276 Cov.: 32

Gnomad AFR AF: 0.0707

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.0779

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.239

GnomAD4 exome AF: 0.245 AC: 97726 AN: 398306 Hom.: 13125 Cov.: 0 AF XY: 0.246 AC XY: 52054 AN XY: 211994

African (AFR) AF: 0.0618 AC: 734 AN: 11882

American (AMR) AF: 0.284 AC: 5899 AN: 20760

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 3308 AN: 12082

East Asian (EAS) AF: 0.0566 AC: 1489 AN: 26294

South Asian (SAS) AF: 0.266 AC: 12645 AN: 47566

European-Finnish (FIN) AF: 0.286 AC: 6749 AN: 23636

Middle Eastern (MID) AF: 0.205 AC: 353 AN: 1718

European-Non Finnish (NFE) AF: 0.263 AC: 61027 AN: 231810

Other (OTH) AF: 0.245 AC: 5522 AN: 22558

GnomAD4 genome AF: 0.216 AC: 32855 AN: 152118 Hom.: 4284 Cov.: 32 AF XY: 0.219 AC XY: 16269 AN XY: 74362

African (AFR) AF: 0.0710 AC: 2950 AN: 41522

American (AMR) AF: 0.284 AC: 4333 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 1009 AN: 3468

East Asian (EAS) AF: 0.0773 AC: 400 AN: 5172

South Asian (SAS) AF: 0.286 AC: 1378 AN: 4822

European-Finnish (FIN) AF: 0.305 AC: 3232 AN: 10584

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.276 AC: 18759 AN: 67954

Other (OTH) AF: 0.240 AC: 506 AN: 2110

Alfa AF: 0.227 Hom.: 684

Bravo AF: 0.206

Asia WGS AF: 0.195 AC: 677 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 20, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.0
DANN	Benign	0.72
PhyloP100		0.48
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs408392; hg19: chr2-113887458; COSMIC: COSV52080108;