2-113119918-G-T

Variant names:

• chr2-113119918-G-T
• rs928940
• ENST00000259206.9:c.11-148G>T

Variant summary

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

The ENST00000259206.9(IL1RN):​c.11-148G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.817 in 713,060 control chromosomes in the GnomAD database, including 243,236 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.78 (46968 hom., cov: 29)
  • Exomes 𝑓: 0.83 (196268 hom.)
• Consequence: IL1RN ENST00000259206.9 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0880
• Publications: 19 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=-0.91).
• BP6: Variant 2-113119918-G-T is Benign according to our data. Variant chr2-113119918-G-T is described in ClinVar as Benign. ClinVar VariationId is 1266807.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.866 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1RN	NM_173841.3	c.11-148G>T		intron_variant	Intron 1 of 5		NP_776213.1
IL1RN	NM_000577.5	c.10+1890G>T		intron_variant	Intron 1 of 4		NP_000568.1
IL1RN	NM_001318914.2	c.-272-148G>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.11-148G>T		intron_variant	Intron 1 of 5	1		ENSP00000259206.5
IL1RN	ENST00000354115.6	c.10+1890G>T		intron_variant	Intron 1 of 4	1		ENSP00000329072.3
IL1RN	ENST00000361779.7	c.-209-1530G>T		intron_variant	Intron 1 of 5	1		ENSP00000354816.3

Frequencies

GnomAD3 genomes AF: 0.777 AC: 117834 AN: 151674 Hom.: 46938 Cov.: 29

Gnomad AFR AF: 0.618

Gnomad AMI AF: 0.846

Gnomad AMR AF: 0.841

Gnomad ASJ AF: 0.883

Gnomad EAS AF: 0.457

Gnomad SAS AF: 0.877

Gnomad FIN AF: 0.753

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.872

Gnomad OTH AF: 0.805

GnomAD4 exome AF: 0.828 AC: 464765 AN: 561268 Hom.: 196268 AF XY: 0.833 AC XY: 248211 AN XY: 297824

African (AFR) AF: 0.617 AC: 9428 AN: 15292

American (AMR) AF: 0.831 AC: 26144 AN: 31462

Ashkenazi Jewish (ASJ) AF: 0.883 AC: 16150 AN: 18290

East Asian (EAS) AF: 0.418 AC: 13142 AN: 31420

South Asian (SAS) AF: 0.884 AC: 51912 AN: 58734

European-Finnish (FIN) AF: 0.762 AC: 36167 AN: 47436

Middle Eastern (MID) AF: 0.848 AC: 2832 AN: 3340

European-Non Finnish (NFE) AF: 0.874 AC: 284214 AN: 325334

Other (OTH) AF: 0.827 AC: 24776 AN: 29960

GnomAD4 genome AF: 0.777 AC: 117911 AN: 151792 Hom.: 46968 Cov.: 29 AF XY: 0.773 AC XY: 57327 AN XY: 74176

African (AFR) AF: 0.618 AC: 25527 AN: 41294

American (AMR) AF: 0.841 AC: 12827 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.883 AC: 3060 AN: 3464

East Asian (EAS) AF: 0.458 AC: 2355 AN: 5142

South Asian (SAS) AF: 0.878 AC: 4227 AN: 4812

European-Finnish (FIN) AF: 0.753 AC: 7929 AN: 10528

Middle Eastern (MID) AF: 0.837 AC: 246 AN: 294

European-Non Finnish (NFE) AF: 0.872 AC: 59266 AN: 67976

Other (OTH) AF: 0.807 AC: 1702 AN: 2110

Alfa AF: 0.759 Hom.: 6154

Bravo AF: 0.771

Asia WGS AF: 0.687 AC: 2389 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

Nov 12, 2018

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	-0.91
CADD	Benign	1.3
DANN	Benign	0.36
PhyloP100		-0.088
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: rs928940; hg19: chr2-113877495; COSMIC: COSV52081479; COSMIC: COSV52081479;