4-141678069-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000585.5(IL15):​c.-100+21762C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 151,912 control chromosomes in the GnomAD database, including 19,913 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.51 ( 19913 hom., cov: 32)

Consequence

IL15
NM_000585.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.819

Publications

7 publications found
Variant links:
Genes affected
IL15 (HGNC:5977): (interleukin 15) The protein encoded by this gene is a cytokine that regulates T and natural killer cell activation and proliferation. This cytokine and interleukine 2 share many biological activities. They are found to bind common hematopoietin receptor subunits, and may compete for the same receptor, and thus negatively regulate each other's activity. The number of CD8+ memory cells is shown to be controlled by a balance between this cytokine and IL2. This cytokine induces the activation of JAK kinases, as well as the phosphorylation and activation of transcription activators STAT3, STAT5, and STAT6. Studies of the mouse counterpart suggested that this cytokine may increase the expression of apoptosis inhibitor BCL2L1/BCL-x(L), possibly through the transcription activation activity of STAT6, and thus prevent apoptosis. Alternatively spliced transcript variants of this gene have been reported. [provided by RefSeq, Feb 2011]

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.826 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IL15NM_000585.5 linkc.-100+21762C>T intron_variant Intron 2 of 7 ENST00000320650.9 NP_000576.1 P40933-1
IL15NM_172175.3 linkc.-501-10753C>T intron_variant Intron 2 of 9 NP_751915.1 P40933-2
IL15NR_037840.3 linkn.764+21762C>T intron_variant Intron 2 of 7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IL15ENST00000320650.9 linkc.-100+21762C>T intron_variant Intron 2 of 7 1 NM_000585.5 ENSP00000323505.4 P40933-1
IL15ENST00000296545.11 linkc.-100+21762C>T intron_variant Intron 2 of 7 1 ENSP00000296545.7 P40933-1
IL15ENST00000529613.5 linkc.-313-10753C>T intron_variant Intron 1 of 7 5 ENSP00000435462.1 P40933-1
IL15ENST00000514653.5 linkc.-501-10753C>T intron_variant Intron 2 of 9 5 ENSP00000422271.1 P40933-2

Frequencies

GnomAD3 genomes
AF:
0.508
AC:
77122
AN:
151794
Hom.:
19906
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.483
Gnomad AMI
AF:
0.558
Gnomad AMR
AF:
0.472
Gnomad ASJ
AF:
0.565
Gnomad EAS
AF:
0.847
Gnomad SAS
AF:
0.631
Gnomad FIN
AF:
0.585
Gnomad MID
AF:
0.437
Gnomad NFE
AF:
0.483
Gnomad OTH
AF:
0.471
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.508
AC:
77159
AN:
151912
Hom.:
19913
Cov.:
32
AF XY:
0.515
AC XY:
38256
AN XY:
74242
show subpopulations
African (AFR)
AF:
0.482
AC:
19962
AN:
41410
American (AMR)
AF:
0.472
AC:
7203
AN:
15262
Ashkenazi Jewish (ASJ)
AF:
0.565
AC:
1959
AN:
3470
East Asian (EAS)
AF:
0.847
AC:
4369
AN:
5158
South Asian (SAS)
AF:
0.631
AC:
3040
AN:
4818
European-Finnish (FIN)
AF:
0.585
AC:
6161
AN:
10538
Middle Eastern (MID)
AF:
0.415
AC:
122
AN:
294
European-Non Finnish (NFE)
AF:
0.483
AC:
32828
AN:
67938
Other (OTH)
AF:
0.476
AC:
1007
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
1902
3805
5707
7610
9512
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
692
1384
2076
2768
3460
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.503
Hom.:
17133
Bravo
AF:
0.496
Asia WGS
AF:
0.698
AC:
2427
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
4.1
DANN
Benign
0.33
PhyloP100
0.82
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs13117878; hg19: chr4-142599222; API