17-80718204-A-G

Variant names:

• chr17-80718204-A-G
• rs6565478
• NM_020761.3:c.507+10205A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020761.3(RPTOR):​c.507+10205A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.663 in 152,058 control chromosomes in the GnomAD database, including 34,010 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 0.66 (34010 hom., cov: 31)
• Consequence: RPTOR NM_020761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.70
• Publications: 5 publications found

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]

ENSG00000299917 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.772 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPTOR	NM_020761.3	c.507+10205A>G		intron_variant	Intron 4 of 33	ENST00000306801.8	NP_065812.1
RPTOR	NM_001163034.2	c.507+10205A>G		intron_variant	Intron 4 of 29		NP_001156506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPTOR	ENST00000306801.8	c.507+10205A>G		intron_variant	Intron 4 of 33	1	NM_020761.3	ENSP00000307272.3

Frequencies

GnomAD3 genomes AF: 0.663 AC: 100753 AN: 151940 Hom.: 33989 Cov.: 31

Gnomad AFR AF: 0.780

Gnomad AMI AF: 0.561

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.685

Gnomad EAS AF: 0.622

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.646

Gnomad OTH AF: 0.665

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.663 AC: 100816 AN: 152058 Hom.: 34010 Cov.: 31 AF XY: 0.655 AC XY: 48690 AN XY: 74318

African (AFR) AF: 0.780 AC: 32330 AN: 41470

American (AMR) AF: 0.516 AC: 7885 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.685 AC: 2374 AN: 3466

East Asian (EAS) AF: 0.622 AC: 3211 AN: 5162

South Asian (SAS) AF: 0.535 AC: 2576 AN: 4812

European-Finnish (FIN) AF: 0.606 AC: 6395 AN: 10554

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.646 AC: 43951 AN: 67994

Other (OTH) AF: 0.662 AC: 1398 AN: 2112

Alfa AF: 0.646 Hom.: 137186

Bravo AF: 0.660

Asia WGS AF: 0.550 AC: 1916 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.18
DANN	Benign	0.38
PhyloP100		-1.7
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

Other links and lift over

dbSNP: rs6565478; hg19: chr17-78692004;