chr2-113128897-A-T

Variant names:

• chr2-113128897-A-T
• rs4252010
• NM_173842.3:c.117-679A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_173842.3(IL1RN):​c.117-679A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0141 in 152,258 control chromosomes in the GnomAD database, including 52 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.014 (52 hom., cov: 32)
• Consequence: IL1RN NM_173842.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.755
• Publications: 1 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: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics, Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0141 (2148/152258) while in subpopulation AFR AF = 0.0491 (2038/41542). AF 95% confidence interval is 0.0473. There are 52 homozygotes in GnomAd4. There are 1015 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 52 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173842.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RN	NM_173842.3	MANE Select	c.117-679A>T		intron	N/A	NP_776214.1	P18510-1
	IL1RN	NM_173841.3		c.126-679A>T		intron	N/A	NP_776213.1	P18510-3
	IL1RN	NM_000577.5		c.63-679A>T		intron	N/A	NP_000568.1	P18510-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RN	ENST00000409930.4	TSL:1 MANE Select	c.117-679A>T		intron	N/A	ENSP00000387173.3	P18510-1
	IL1RN	ENST00000259206.9	TSL:1	c.126-679A>T		intron	N/A	ENSP00000259206.5	P18510-3
	IL1RN	ENST00000354115.6	TSL:1	c.63-679A>T		intron	N/A	ENSP00000329072.3	P18510-2

Frequencies

GnomAD3 genomes AF: 0.0141 AC: 2145 AN: 152140 Hom.: 51 Cov.: 32

Gnomad AFR AF: 0.0491

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00530

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.0100

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

GnomAD4 genome AF: 0.0141 AC: 2148 AN: 152258 Hom.: 52 Cov.: 32 AF XY: 0.0136 AC XY: 1015 AN XY: 74452

African (AFR) AF: 0.0491 AC: 2038 AN: 41542

American (AMR) AF: 0.00523 AC: 80 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68018

Other (OTH) AF: 0.00994 AC: 21 AN: 2112

Alfa AF: 0.0112 Hom.: 4

Bravo AF: 0.0165

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.8
DANN	Benign	0.47
PhyloP100		0.76
Mutation Taster		=100/0	polymorphism

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: rs4252010; hg19: chr2-113886474;