chr5-159314825-AAAAT-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BS1_Supporting

The NM_002187.3(IL12B):​c.*1272_*1275del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00255 in 152,362 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0025 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

IL12B
NM_002187.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.780
Variant links:
Genes affected
IL12B (HGNC:5970): (interleukin 12B) This gene encodes a subunit of interleukin 12, a cytokine that acts on T and natural killer cells, and has a broad array of biological activities. Interleukin 12 is a disulfide-linked heterodimer composed of the 40 kD cytokine receptor like subunit encoded by this gene, and a 35 kD subunit encoded by IL12A. This cytokine is expressed by activated macrophages that serve as an essential inducer of Th1 cells development. This cytokine has been found to be important for sustaining a sufficient number of memory/effector Th1 cells to mediate long-term protection to an intracellular pathogen. Overexpression of this gene was observed in the central nervous system of patients with multiple sclerosis (MS), suggesting a role of this cytokine in the pathogenesis of the disease. The promoter polymorphism of this gene has been reported to be associated with the severity of atopic and non-atopic asthma in children. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00255 (388/152362) while in subpopulation AFR AF= 0.0089 (370/41584). AF 95% confidence interval is 0.00815. There are 1 homozygotes in gnomad4. There are 174 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
IL12BNM_002187.3 linkuse as main transcriptc.*1272_*1275del 3_prime_UTR_variant 8/8 ENST00000231228.3
LOC105377683XR_941138.3 linkuse as main transcriptn.401-377_401-374del intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IL12BENST00000231228.3 linkuse as main transcriptc.*1272_*1275del 3_prime_UTR_variant 8/81 NM_002187.3 P1
IL12BENST00000696750.1 linkuse as main transcriptc.*1272_*1275del 3_prime_UTR_variant 5/5
IL12BENST00000696751.1 linkuse as main transcriptc.*1754_*1757del 3_prime_UTR_variant, NMD_transcript_variant 7/7
ENST00000521472.6 linkuse as main transcriptn.289+3427_289+3430del intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
AF:
0.00255
AC:
388
AN:
152244
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00892
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000523
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.00191
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
132
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
74
Gnomad4 EAS exome
AF:
0.00
GnomAD4 genome
AF:
0.00255
AC:
388
AN:
152362
Hom.:
1
Cov.:
32
AF XY:
0.00234
AC XY:
174
AN XY:
74518
show subpopulations
Gnomad4 AFR
AF:
0.00890
Gnomad4 AMR
AF:
0.000523
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.00189
Bravo
AF:
0.00273

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Familial Atypical Mycobacteriosis, Autosomal Recessive Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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: rs886060351; hg19: chr5-158741833; API