2-113118042-A-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6_ModerateBS1

The NM_173841.3(IL1RN):​c.10+14A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000248 in 1,611,104 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 0.00014 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

IL1RN
NM_173841.3 intron

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.408
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 Benign. Variant got -8 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 2-113118042-A-C is Benign according to our data. Variant chr2-113118042-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 2050355.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000138 (21/152214) while in subpopulation AFR AF= 0.000506 (21/41526). AF 95% confidence interval is 0.000338. There are 0 homozygotes in gnomad4. There are 12 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IL1RNNM_173841.3 linkc.10+14A>C intron_variant Intron 1 of 5 NP_776213.1 P18510-3
IL1RNNM_000577.5 linkc.10+14A>C intron_variant Intron 1 of 4 NP_000568.1 P18510-2
IL1RNNM_001318914.2 linkc.-273+14A>C 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+14A>C intron_variant Intron 1 of 5 1 ENSP00000259206.5 P18510-3
IL1RNENST00000354115.6 linkc.10+14A>C intron_variant Intron 1 of 4 1 ENSP00000329072.3 P18510-2
IL1RNENST00000361779.7 linkc.-210+14A>C intron_variant Intron 1 of 5 1 ENSP00000354816.3 P18510-4

Frequencies

GnomAD3 genomes
AF:
0.000131
AC:
20
AN:
152096
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000483
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000278
AC:
7
AN:
251482
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135916
show subpopulations
Gnomad AFR exome
AF:
0.000369
Gnomad AMR exome
AF:
0.0000289
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000130
AC:
19
AN:
1458890
Hom.:
0
Cov.:
29
AF XY:
0.0000165
AC XY:
12
AN XY:
725904
show subpopulations
Gnomad4 AFR exome
AF:
0.000448
Gnomad4 AMR exome
AF:
0.0000224
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:
0.00
Gnomad4 OTH exome
AF:
0.0000332
GnomAD4 genome
AF:
0.000138
AC:
21
AN:
152214
Hom.:
0
Cov.:
33
AF XY:
0.000161
AC XY:
12
AN XY:
74422
show subpopulations
Gnomad4 AFR
AF:
0.000506
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:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.000181
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

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
Dec 07, 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
-0.82
CADD
Benign
5.1
DANN
Benign
0.86

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: rs753071748; hg19: chr2-113875619; API