chr2-113118036-C-T

Variant summary

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

The NM_173841.3(IL1RN):​c.10+8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Consequence

IL1RN
NM_173841.3 splice_region, intron

Scores

2
Splicing: ADA: 0.0002066
2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0370
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
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.64).
BP6
Variant 2-113118036-C-T is Benign according to our data. Variant chr2-113118036-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3661850.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IL1RNNM_173841.3 linkc.10+8C>T splice_region_variant, intron_variant Intron 1 of 5 NP_776213.1 P18510-3
IL1RNNM_000577.5 linkc.10+8C>T splice_region_variant, intron_variant Intron 1 of 4 NP_000568.1 P18510-2
IL1RNNM_001318914.2 linkc.-273+8C>T splice_region_variant, intron_variant Intron 1 of 6 NP_001305843.1 P18510-4A0A024R528

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IL1RNENST00000259206.9 linkc.10+8C>T splice_region_variant, intron_variant Intron 1 of 5 1 ENSP00000259206.5 P18510-3
IL1RNENST00000354115.6 linkc.10+8C>T splice_region_variant, intron_variant Intron 1 of 4 1 ENSP00000329072.3 P18510-2
IL1RNENST00000361779.7 linkc.-210+8C>T splice_region_variant, intron_variant Intron 1 of 5 1 ENSP00000354816.3 P18510-4

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
29
GnomAD4 genome
Cov.:
33

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
Aug 09, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.64
CADD
Benign
9.6
DANN
Benign
0.82

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00021
dbscSNV1_RF
Benign
0.0020

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-113875613; API