chr17-80731492-G-A

Variant summary

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

The NM_020761.3(RPTOR):​c.654+786G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 152,122 control chromosomes in the GnomAD database, including 2,902 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 0.18 ( 2902 hom., cov: 32)

Consequence

RPTOR
NM_020761.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.508

Publications

4 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=-0.9).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RPTORNM_020761.3 linkc.654+786G>A intron_variant Intron 5 of 33 ENST00000306801.8 NP_065812.1 Q8N122-1Q6DKI0
RPTORNM_001163034.2 linkc.654+786G>A intron_variant Intron 5 of 29 NP_001156506.1 Q8N122-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RPTORENST00000306801.8 linkc.654+786G>A intron_variant Intron 5 of 33 1 NM_020761.3 ENSP00000307272.3 Q8N122-1

Frequencies

GnomAD3 genomes
AF:
0.179
AC:
27282
AN:
152004
Hom.:
2905
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0589
Gnomad AMI
AF:
0.203
Gnomad AMR
AF:
0.191
Gnomad ASJ
AF:
0.200
Gnomad EAS
AF:
0.241
Gnomad SAS
AF:
0.211
Gnomad FIN
AF:
0.198
Gnomad MID
AF:
0.199
Gnomad NFE
AF:
0.239
Gnomad OTH
AF:
0.199
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.179
AC:
27275
AN:
152122
Hom.:
2902
Cov.:
32
AF XY:
0.179
AC XY:
13279
AN XY:
74352
show subpopulations
African (AFR)
AF:
0.0589
AC:
2445
AN:
41536
American (AMR)
AF:
0.190
AC:
2910
AN:
15280
Ashkenazi Jewish (ASJ)
AF:
0.200
AC:
695
AN:
3470
East Asian (EAS)
AF:
0.241
AC:
1244
AN:
5172
South Asian (SAS)
AF:
0.210
AC:
1012
AN:
4812
European-Finnish (FIN)
AF:
0.198
AC:
2087
AN:
10566
Middle Eastern (MID)
AF:
0.204
AC:
60
AN:
294
European-Non Finnish (NFE)
AF:
0.239
AC:
16223
AN:
67970
Other (OTH)
AF:
0.196
AC:
414
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
1138
2276
3415
4553
5691
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
294
588
882
1176
1470
<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:
0.222
Hom.:
1998
Bravo
AF:
0.172
Asia WGS
AF:
0.164
AC:
573
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
1.4
DANN
Benign
0.61
PhyloP100
-0.51
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: rs12603074; hg19: chr17-78705292; API