rs9890502

Positions:

• chr17-80617225-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020761.3(RPTOR):​c.163-8466C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 152,036 control chromosomes in the GnomAD database, including 6,462 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 0.29 (6462 hom., cov: 32)
• Consequence: RPTOR NM_020761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.916

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPTOR	NM_020761.3	c.163-8466C>T		intron_variant		ENST00000306801.8	NP_065812.1
RPTOR	NM_001163034.2	c.163-8466C>T		intron_variant			NP_001156506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPTOR	ENST00000306801.8	c.163-8466C>T		intron_variant		1	NM_020761.3	ENSP00000307272.3

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43884 AN: 151918 Hom.: 6459 Cov.: 32

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.320

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

GnomAD4 genome AF: 0.289 AC: 43896 AN: 152036 Hom.: 6462 Cov.: 32 AF XY: 0.289 AC XY: 21496 AN XY: 74328

Gnomad4 AFR AF: 0.283

Gnomad4 AMR AF: 0.231

Gnomad4 ASJ AF: 0.427

Gnomad4 EAS AF: 0.262

Gnomad4 SAS AF: 0.266

Gnomad4 FIN AF: 0.326

Gnomad4 NFE AF: 0.295

Gnomad4 OTH AF: 0.322

Alfa AF: 0.296 Hom.: 13856

Bravo AF: 0.284

Asia WGS AF: 0.276 AC: 960 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.6
DANN	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs9890502; hg19: chr17-78591025;