rs2280147

Variant names:

• chr17-80902427-C-T
• rs2280147
• NM_020761.3:c.2402-6384C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RPTOR	NM_020761.3	c.2402-6384C>T		intron_variant	Intron 20 of 33	ENST00000306801.8	NP_065812.1
RPTOR	NM_001163034.2	c.1928-6384C>T		intron_variant	Intron 16 of 29		NP_001156506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPTOR	ENST00000306801.8	c.2402-6384C>T		intron_variant	Intron 20 of 33	1	NM_020761.3	ENSP00000307272.3

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

African (AFR) AF: 0.542 AC: 22485 AN: 41472

American (AMR) AF: 0.743 AC: 11371 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.742 AC: 2577 AN: 3472

East Asian (EAS) AF: 0.704 AC: 3633 AN: 5160

South Asian (SAS) AF: 0.613 AC: 2952 AN: 4818

European-Finnish (FIN) AF: 0.738 AC: 7823 AN: 10600

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.764 AC: 51924 AN: 67994

Other (OTH) AF: 0.667 AC: 1409 AN: 2112

Alfa AF: 0.720 Hom.: 11530

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
PhyloP100		-0.73
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: rs2280147; hg19: chr17-78876227;