chr15-74039318-A-C
Variant names:
Variant summary
Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_033238.3(PML):c.1711-3671A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 152,212 control chromosomes in the GnomAD database, including 2,339 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 0.17 ( 2339 hom., cov: 33)
Consequence
PML
NM_033238.3 intron
NM_033238.3 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.229
Publications
10 publications found
Genes affected
PML (HGNC:9113): (PML nuclear body scaffold) The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. This phosphoprotein localizes to nuclear bodies where it functions as a transcription factor and tumor suppressor. Its expression is cell-cycle related and it regulates the p53 response to oncogenic signals. The gene is often involved in the translocation with the retinoic acid receptor alpha gene associated with acute promyelocytic leukemia (APL). Extensive alternative splicing of this gene results in several variations of the protein's central and C-terminal regions; all variants encode the same N-terminus. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]
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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 (NFE) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PML | NM_033238.3 | c.1711-3671A>C | intron_variant | Intron 7 of 8 | ENST00000268058.8 | NP_150241.2 | ||
PML | NM_002675.4 | c.1711-3671A>C | intron_variant | Intron 7 of 7 | NP_002666.1 | |||
PML | NM_033249.3 | c.1567-3671A>C | intron_variant | Intron 6 of 6 | NP_150252.1 | |||
PML | NM_033246.3 | c.*36-3671A>C | intron_variant | Intron 5 of 5 | NP_150249.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.166 AC: 25319AN: 152094Hom.: 2341 Cov.: 33 show subpopulations
GnomAD3 genomes
AF:
AC:
25319
AN:
152094
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome AF: 0.166 AC: 25321AN: 152212Hom.: 2339 Cov.: 33 AF XY: 0.166 AC XY: 12319AN XY: 74394 show subpopulations
GnomAD4 genome
AF:
AC:
25321
AN:
152212
Hom.:
Cov.:
33
AF XY:
AC XY:
12319
AN XY:
74394
show subpopulations
African (AFR)
AF:
AC:
5517
AN:
41528
American (AMR)
AF:
AC:
1667
AN:
15302
Ashkenazi Jewish (ASJ)
AF:
AC:
269
AN:
3472
East Asian (EAS)
AF:
AC:
705
AN:
5180
South Asian (SAS)
AF:
AC:
656
AN:
4824
European-Finnish (FIN)
AF:
AC:
2818
AN:
10576
Middle Eastern (MID)
AF:
AC:
23
AN:
294
European-Non Finnish (NFE)
AF:
AC:
13335
AN:
68012
Other (OTH)
AF:
AC:
271
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
1071
2142
3213
4284
5355
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Genome Het
Genome Hom
Variant carriers
0
276
552
828
1104
1380
<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:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
500
AN:
3478
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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