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2-113120050-A-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The ENST00000259206.9(IL1RN):c.11-16A>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000298 in 1,609,922 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

IL1RN
ENST00000259206.9 splice_polypyrimidine_tract, intron

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.730
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 2-113120050-A-C is Benign according to our data. Variant chr2-113120050-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 1595653.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
IL1RNNM_000577.5 linkuse as main transcriptc.10+2022A>C intron_variant
IL1RNNM_001318914.2 linkuse as main transcriptc.-272-16A>C splice_polypyrimidine_tract_variant, intron_variant
IL1RNNM_173841.3 linkuse as main transcriptc.11-16A>C splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IL1RNENST00000259206.9 linkuse as main transcriptc.11-16A>C splice_polypyrimidine_tract_variant, intron_variant 1 P18510-3
IL1RNENST00000354115.6 linkuse as main transcriptc.10+2022A>C intron_variant 1 A1P18510-2
IL1RNENST00000361779.7 linkuse as main transcriptc.-209-1398A>C intron_variant 1 P18510-4

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00000658
AC:
1
AN:
151996
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000802
AC:
2
AN:
249242
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
134754
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000178
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000322
AC:
47
AN:
1457926
Hom.:
0
Cov.:
30
AF XY:
0.0000303
AC XY:
22
AN XY:
725510
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000424
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00000658
AC:
1
AN:
151996
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
74224
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Sterile multifocal osteomyelitis with periostitis and pustulosis Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeFeb 20, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
Cadd
Benign
0.24
Dann
Benign
0.72

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.

Other links and lift over

dbSNP: rs747837384; hg19: chr2-113877627; API