rs2280147

Positions:

• chr17-80902427-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.2402-6384C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.691 in 152,138 control chromosomes in the GnomAD database, including 37,082 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 0.69 (37082 hom., cov: 34)
• Consequence: RPTOR NM_020761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.729

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=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPTOR	NM_020761.3	c.2402-6384C>T		intron_variant		ENST00000306801.8
RPTOR	NM_001163034.2	c.1928-6384C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPTOR	ENST00000306801.8	c.2402-6384C>T		intron_variant		1	NM_020761.3	P1

Frequencies

GnomAD3 genomes AF: 0.691 AC: 105052 AN: 152020 Hom.: 37055 Cov.: 34

Gnomad AFR AF: 0.542

Gnomad AMI AF: 0.833

Gnomad AMR AF: 0.742

Gnomad ASJ AF: 0.742

Gnomad EAS AF: 0.704

Gnomad SAS AF: 0.611

Gnomad FIN AF: 0.738

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.764

Gnomad OTH AF: 0.674

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

GnomAD4 genome AF: 0.691 AC: 105121 AN: 152138 Hom.: 37082 Cov.: 34 AF XY: 0.690 AC XY: 51348 AN XY: 74406

Gnomad4 AFR AF: 0.542

Gnomad4 AMR AF: 0.743

Gnomad4 ASJ AF: 0.742

Gnomad4 EAS AF: 0.704

Gnomad4 SAS AF: 0.613

Gnomad4 FIN AF: 0.738

Gnomad4 NFE AF: 0.764

Gnomad4 OTH AF: 0.667

Alfa AF: 0.720 Hom.: 4945

Bravo AF: 0.687

Asia WGS AF: 0.617 AC: 2144 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	0.70
DANN	Benign	0.56

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

LitVar

Other links and lift over

dbSNP: rs2280147; hg19: chr17-78876227;