rs4251985

Variant names:

• chr2-113119836-G-T
• rs4251985
• ENST00000259206.9:c.11-230G>T

Variant summary

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

The ENST00000259206.9(IL1RN):​c.11-230G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 152,092 control chromosomes in the GnomAD database, including 4,107 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.21 (4107 hom., cov: 32)
• Consequence: IL1RN ENST00000259206.9 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.153
• Publications: 13 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=-0.84).
• BP6: Variant 2-113119836-G-T is Benign according to our data. Variant chr2-113119836-G-T is described in ClinVar as Benign. ClinVar VariationId is 1232909.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1RN	NM_173841.3	c.11-230G>T		intron_variant	Intron 1 of 5		NP_776213.1
IL1RN	NM_000577.5	c.10+1808G>T		intron_variant	Intron 1 of 4		NP_000568.1
IL1RN	NM_001318914.2	c.-272-230G>T		intron_variant	Intron 1 of 6		NP_001305843.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1RN	ENST00000259206.9	c.11-230G>T		intron_variant	Intron 1 of 5	1		ENSP00000259206.5
IL1RN	ENST00000354115.6	c.10+1808G>T		intron_variant	Intron 1 of 4	1		ENSP00000329072.3
IL1RN	ENST00000361779.7	c.-209-1612G>T		intron_variant	Intron 1 of 5	1		ENSP00000354816.3

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31888 AN: 151974 Hom.: 4101 Cov.: 32

Gnomad AFR AF: 0.0609

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.0971

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.229

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

GnomAD4 genome AF: 0.210 AC: 31904 AN: 152092 Hom.: 4107 Cov.: 32 AF XY: 0.212 AC XY: 15791 AN XY: 74330

African (AFR) AF: 0.0607 AC: 2521 AN: 41512

American (AMR) AF: 0.275 AC: 4208 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 993 AN: 3468

East Asian (EAS) AF: 0.0966 AC: 500 AN: 5176

South Asian (SAS) AF: 0.287 AC: 1380 AN: 4816

European-Finnish (FIN) AF: 0.305 AC: 3221 AN: 10552

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

European-Non Finnish (NFE) AF: 0.269 AC: 18307 AN: 67976

Other (OTH) AF: 0.231 AC: 487 AN: 2112

Alfa AF: 0.253 Hom.: 6681

Bravo AF: 0.199

Asia WGS AF: 0.197 AC: 684 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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.5
DANN	Benign	0.78
PhyloP100		0.15
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4251985; hg19: chr2-113877413;