2-113119836-G-T

Position:

• chr2-113119836-G-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.84).
• BP6: Variant 2-113119836-G-T is Benign according to our data. Variant chr2-113119836-G-T is described in ClinVar as [Benign]. Clinvar id 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/exons	MANE	Protein	UniProt
IL1RN	NM_000577.5	c.10+1808G>T		intron_variant			NP_000568.1
IL1RN	NM_001318914.2	c.-272-230G>T		intron_variant			NP_001305843.1
IL1RN	NM_173841.3	c.11-230G>T		intron_variant			NP_776213.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL1RN	ENST00000259206.9	c.11-230G>T		intron_variant		1		ENSP00000259206
IL1RN	ENST00000354115.6	c.10+1808G>T		intron_variant		1		ENSP00000329072	A1
IL1RN	ENST00000361779.7	c.-209-1612G>T		intron_variant		1		ENSP00000354816

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

Gnomad4 AFR AF: 0.0607

Gnomad4 AMR AF: 0.275

Gnomad4 ASJ AF: 0.286

Gnomad4 EAS AF: 0.0966

Gnomad4 SAS AF: 0.287

Gnomad4 FIN AF: 0.305

Gnomad4 NFE AF: 0.269

Gnomad4 OTH AF: 0.231

Alfa AF: 0.259 Hom.: 5368

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

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	-0.84
CADD	Benign	4.5
DANN	Benign	0.78

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4251985; hg19: chr2-113877413;