NM_020761.3:c.162+4816G>A

Variant summary

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

The NM_020761.3(RPTOR):​c.162+4816G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 152,012 control chromosomes in the GnomAD database, including 29,806 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 0.62 ( 29806 hom., cov: 32)

Consequence

RPTOR
NM_020761.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.50

Publications

8 publications found
Variant links:
Genes affected
RPTOR (HGNC:30287): (regulatory associated protein of MTOR complex 1) This gene encodes a component of a signaling pathway that regulates cell growth in response to nutrient and insulin levels. The encoded protein forms a stoichiometric complex with the mTOR kinase, and also associates with eukaryotic initiation factor 4E-binding protein-1 and ribosomal protein S6 kinase. The protein positively regulates the downstream effector ribosomal protein S6 kinase, and negatively regulates the mTOR kinase. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

Genome browser will be placed here

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=-0.93).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.699 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RPTORNM_020761.3 linkc.162+4816G>A intron_variant Intron 1 of 33 ENST00000306801.8 NP_065812.1 Q8N122-1Q6DKI0
RPTORNM_001163034.2 linkc.162+4816G>A intron_variant Intron 1 of 29 NP_001156506.1 Q8N122-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RPTORENST00000306801.8 linkc.162+4816G>A intron_variant Intron 1 of 33 1 NM_020761.3 ENSP00000307272.3 Q8N122-1

Frequencies

GnomAD3 genomes
AF:
0.618
AC:
93920
AN:
151894
Hom.:
29810
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.503
Gnomad AMI
AF:
0.652
Gnomad AMR
AF:
0.541
Gnomad ASJ
AF:
0.745
Gnomad EAS
AF:
0.584
Gnomad SAS
AF:
0.526
Gnomad FIN
AF:
0.635
Gnomad MID
AF:
0.715
Gnomad NFE
AF:
0.704
Gnomad OTH
AF:
0.657
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.618
AC:
93933
AN:
152012
Hom.:
29806
Cov.:
32
AF XY:
0.613
AC XY:
45529
AN XY:
74302
show subpopulations
African (AFR)
AF:
0.502
AC:
20813
AN:
41436
American (AMR)
AF:
0.540
AC:
8246
AN:
15262
Ashkenazi Jewish (ASJ)
AF:
0.745
AC:
2582
AN:
3468
East Asian (EAS)
AF:
0.583
AC:
3012
AN:
5168
South Asian (SAS)
AF:
0.527
AC:
2538
AN:
4816
European-Finnish (FIN)
AF:
0.635
AC:
6715
AN:
10572
Middle Eastern (MID)
AF:
0.714
AC:
210
AN:
294
European-Non Finnish (NFE)
AF:
0.704
AC:
47847
AN:
67976
Other (OTH)
AF:
0.652
AC:
1378
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
1786
3572
5358
7144
8930
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
766
1532
2298
3064
3830
<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:
0.673
Hom.:
17795
Bravo
AF:
0.606
Asia WGS
AF:
0.529
AC:
1843
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.93
CADD
Benign
3.0
DANN
Benign
0.84
PhyloP100
-1.5
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: rs9911978; hg19: chr17-78524407; API