2-113117640-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The XM_047444185.1(IL1RN):c.-298A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 399,516 control chromosomes in the GnomAD database, including 9,897 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.21 (4101 hom., cov: 33)
  • Exomes 𝑓: 0.20 (5796 hom.)
• Consequence: IL1RN XM_047444185.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.28

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 2-113117640-A-C is Benign according to our data. Variant chr2-113117640-A-C is described in ClinVar as [Benign]. Clinvar id is 1249883.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1RN	XM_047444185.1	c.-298A>C		5_prime_UTR_variant	4/10
IL1RN	XM_011511121.2	c.-272-2426A>C		intron_variant
IL1RN	XM_047444184.1	c.-272-2426A>C		intron_variant
IL1RN	XM_047444186.1	c.-209-3808A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1RN	ENST00000465812.6	n.750A>C		non_coding_transcript_exon_variant	5/6	5
IL1RN	ENST00000409052.6	c.-272-2426A>C		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31855 AN: 152122 Hom.: 4095 Cov.: 33

Gnomad AFR AF: 0.0583

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.0975

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.231

GnomAD4 exome AF: 0.205 AC: 50645 AN: 247276 Hom.: 5796 Cov.: 0 AF XY: 0.205 AC XY: 26300 AN XY: 128232

Gnomad4 AFR exome AF: 0.0431

Gnomad4 AMR exome AF: 0.260

Gnomad4 ASJ exome AF: 0.237

Gnomad4 EAS exome AF: 0.0656

Gnomad4 SAS exome AF: 0.228

Gnomad4 FIN exome AF: 0.230

Gnomad4 NFE exome AF: 0.220

Gnomad4 OTH exome AF: 0.205

GnomAD4 genome AF: 0.209 AC: 31870 AN: 152240 Hom.: 4101 Cov.: 33 AF XY: 0.212 AC XY: 15811 AN XY: 74426

Gnomad4 AFR AF: 0.0582

Gnomad4 AMR AF: 0.278

Gnomad4 ASJ AF: 0.294

Gnomad4 EAS AF: 0.0970

Gnomad4 SAS AF: 0.284

Gnomad4 FIN AF: 0.305

Gnomad4 NFE AF: 0.269

Gnomad4 OTH AF: 0.232

Alfa AF: 0.125 Hom.: 301

Bravo AF: 0.199

Asia WGS AF: 0.195 AC: 680 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.036
Dann	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4251968; hg19: chr2-113875217; COSMIC: COSV52079906; COSMIC: COSV52079906;