2-113118176-C-G

Position:

• chr2-113118176-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000259206.9(IL1RN):​c.10+148C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 1,262,988 control chromosomes in the GnomAD database, including 41,060 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (4051 hom., cov: 33)
  • Exomes 𝑓: 0.25 (37009 hom.)
• Consequence: IL1RN ENST00000259206.9 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.300

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 2-113118176-C-G is Benign according to our data. Variant chr2-113118176-C-G is described in ClinVar as [Benign]. Clinvar id is 1258566.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL1RN	NM_000577.5	c.10+148C>G		intron_variant			NP_000568.1
IL1RN	NM_001318914.2	c.-273+148C>G		intron_variant			NP_001305843.1
IL1RN	NM_173841.3	c.10+148C>G		intron_variant			NP_776213.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL1RN	ENST00000259206.9	c.10+148C>G		intron_variant		1		ENSP00000259206
IL1RN	ENST00000354115.6	c.10+148C>G		intron_variant		1		ENSP00000329072	A1
IL1RN	ENST00000361779.7	c.-210+148C>G		intron_variant		1		ENSP00000354816

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31756 AN: 151988 Hom.: 4045 Cov.: 33

Gnomad AFR AF: 0.0584

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.0971

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.231

GnomAD4 exome AF: 0.248 AC: 275516 AN: 1110882 Hom.: 37009 AF XY: 0.249 AC XY: 140399 AN XY: 563472

Gnomad4 AFR exome AF: 0.0459

Gnomad4 AMR exome AF: 0.312

Gnomad4 ASJ exome AF: 0.284

Gnomad4 EAS exome AF: 0.0812

Gnomad4 SAS exome AF: 0.271

Gnomad4 FIN exome AF: 0.284

Gnomad4 NFE exome AF: 0.255

Gnomad4 OTH exome AF: 0.240

GnomAD4 genome AF: 0.209 AC: 31771 AN: 152106 Hom.: 4051 Cov.: 33 AF XY: 0.212 AC XY: 15741 AN XY: 74344

Gnomad4 AFR AF: 0.0582

Gnomad4 AMR AF: 0.278

Gnomad4 ASJ AF: 0.292

Gnomad4 EAS AF: 0.0966

Gnomad4 SAS AF: 0.283

Gnomad4 FIN AF: 0.303

Gnomad4 NFE AF: 0.269

Gnomad4 OTH AF: 0.233

Alfa AF: 0.235 Hom.: 646

Bravo AF: 0.199

Asia WGS AF: 0.195 AC: 679 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 12, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.8
DANN	Benign	0.29

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4251969; hg19: chr2-113875753; COSMIC: COSV52079936; COSMIC: COSV52079936;