chr2-113131002-T-C

Variant names:

• chr2-113131002-T-C
• rs432014
• NM_173842.3:c.206-43T>C

Variant summary

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

The NM_173842.3(IL1RN):​c.206-43T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 1,227,456 control chromosomes in the GnomAD database, including 44,853 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (4757 hom., cov: 31)
  • Exomes 𝑓: 0.27 (40096 hom.)
• Consequence: IL1RN NM_173842.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.313
• Publications: 15 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=-0.93).
• BP6: Variant 2-113131002-T-C is Benign according to our data. Variant chr2-113131002-T-C is described in ClinVar as Benign. ClinVar VariationId is 1294753.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1RN	NM_173842.3	c.206-43T>C		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.206-43T>C		intron_variant	Intron 2 of 3	1	NM_173842.3	ENSP00000387173.3

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36823 AN: 151880 Hom.: 4746 Cov.: 31

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.0777

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.229

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.255

GnomAD2 exomes AF: 0.264 AC: 66127 AN: 250134 AF XY: 0.265

Gnomad AFR exome AF: 0.164

Gnomad AMR exome AF: 0.330

Gnomad ASJ exome AF: 0.298

Gnomad EAS exome AF: 0.0704

Gnomad FIN exome AF: 0.304

Gnomad NFE exome AF: 0.273

Gnomad OTH exome AF: 0.270

GnomAD4 exome AF: 0.265 AC: 285406 AN: 1075458 Hom.: 40096 Cov.: 15 AF XY: 0.265 AC XY: 146700 AN XY: 552730

African (AFR) AF: 0.164 AC: 4288 AN: 26090

American (AMR) AF: 0.326 AC: 14400 AN: 44162

Ashkenazi Jewish (ASJ) AF: 0.290 AC: 6905 AN: 23786

East Asian (EAS) AF: 0.0594 AC: 2260 AN: 38060

South Asian (SAS) AF: 0.283 AC: 22260 AN: 78528

European-Finnish (FIN) AF: 0.299 AC: 15854 AN: 53068

Middle Eastern (MID) AF: 0.218 AC: 1101 AN: 5042

European-Non Finnish (NFE) AF: 0.271 AC: 206028 AN: 759194

Other (OTH) AF: 0.259 AC: 12310 AN: 47528

GnomAD4 genome AF: 0.243 AC: 36865 AN: 151998 Hom.: 4757 Cov.: 31 AF XY: 0.244 AC XY: 18137 AN XY: 74266

African (AFR) AF: 0.165 AC: 6863 AN: 41502

American (AMR) AF: 0.293 AC: 4474 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 1010 AN: 3472

East Asian (EAS) AF: 0.0771 AC: 399 AN: 5172

South Asian (SAS) AF: 0.292 AC: 1404 AN: 4816

European-Finnish (FIN) AF: 0.303 AC: 3193 AN: 10538

Middle Eastern (MID) AF: 0.226 AC: 66 AN: 292

European-Non Finnish (NFE) AF: 0.275 AC: 18691 AN: 67924

Other (OTH) AF: 0.256 AC: 541 AN: 2114

Alfa AF: 0.252 Hom.: 1399

Bravo AF: 0.238

Asia WGS AF: 0.202 AC: 701 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

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

- -

May 12, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 50% of patients studied by a panel of primary immunodeficiencies. Number of patients: 48. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	7.7
DANN	Benign	0.74
PhyloP100		0.31
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: rs432014; hg19: chr2-113888579; COSMIC: COSV52080154; COSMIC: COSV52080154;