Variant chr2-113117640-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The XM_047444185.1(IL1RN):c.-298A>C variant causes a 5 prime UTR premature start codon gain 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_premature_start_codon_gain

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.28

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_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	Effect	Exon rank	Protein	UniProt
IL1RN	XM_047444185.1 link	c.-298A>C	5_prime_UTR_premature_start_codon_gain_variant	Exon 4 of 10	XP_047300141.1
IL1RN	XM_047444185.1 link	c.-298A>C	5_prime_UTR_variant	Exon 4 of 10	XP_047300141.1
IL1RN	XM_011511121.2 link	c.-272-2426A>C	intron_variant	Intron 3 of 8	XP_011509423.1	P18510-4A0A024R528

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1RN	ENST00000465812.6 link	n.750A>C		non_coding_transcript_exon_variant	Exon 5 of 6	5
IL1RN	ENST00000409052.6 link	n.-272-2426A>C		intron_variant	Intron 3 of 9	5		ENSP00000387210.1		P18510-4

Frequencies

GnomAD3 genomes

AF:

0.209

AC:

31855

AN:

152122

Hom.:

4095

Cov.:

show subpopulations

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.:

AF XY:

0.205

AC XY:

26300

AN XY:

128232

show subpopulations

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.:

AF XY:

0.212

AC XY:

15811

AN XY:

74426

show subpopulations

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 19, 2021

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

-0.85

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over