2-113131429-T-G

Variant names:

• chr2-113131429-T-G
• rs431726
• NM_173842.3:c.318+272T>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_173842.3(IL1RN):​c.318+272T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 152,096 control chromosomes in the GnomAD database, including 4,308 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.23 (4308 hom., cov: 31)
• Consequence: IL1RN NM_173842.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.260
• Publications: 10 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 2-113131429-T-G is Benign according to our data. Variant chr2-113131429-T-G is described in ClinVar as Benign. ClinVar VariationId is 1264174.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1RN	NM_173842.3	c.318+272T>G		intron_variant	Intron 3 of 3	ENST00000409930.4	NP_776214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1RN	ENST00000409930.4	c.318+272T>G		intron_variant	Intron 3 of 3	1	NM_173842.3	ENSP00000387173.3

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34184 AN: 151978 Hom.: 4297 Cov.: 31

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.0773

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.244

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

GnomAD4 genome AF: 0.225 AC: 34229 AN: 152096 Hom.: 4308 Cov.: 31 AF XY: 0.227 AC XY: 16869 AN XY: 74354

African (AFR) AF: 0.126 AC: 5245 AN: 41508

American (AMR) AF: 0.282 AC: 4303 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 966 AN: 3470

East Asian (EAS) AF: 0.0767 AC: 397 AN: 5174

South Asian (SAS) AF: 0.276 AC: 1330 AN: 4820

European-Finnish (FIN) AF: 0.304 AC: 3213 AN: 10562

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.264 AC: 17974 AN: 67972

Other (OTH) AF: 0.245 AC: 516 AN: 2106

Alfa AF: 0.247 Hom.: 6271

Bravo AF: 0.218

Asia WGS AF: 0.194 AC: 675 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 19, 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	-0.89
CADD	Benign	5.8
DANN	Benign	0.47
PhyloP100		0.26
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs431726; hg19: chr2-113889006; COSMIC: COSV52080167; COSMIC: COSV52080167;