rs2048753

Variant names:

• chr17-80815488-G-A
• rs2048753
• NM_020761.3:c.891-6713G>A

Variant summary

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

The NM_020761.3(RPTOR):​c.891-6713G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 152,276 control chromosomes in the GnomAD database, including 3,679 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 0.20 (3679 hom., cov: 33)
• Consequence: RPTOR NM_020761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.869
• Publications: 9 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020761.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPTOR	NM_020761.3	MANE Select	c.891-6713G>A		intron	N/A	NP_065812.1	Q8N122-1
	RPTOR	NM_001163034.2		c.891-6713G>A		intron	N/A	NP_001156506.1	Q8N122-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPTOR	ENST00000306801.8	TSL:1 MANE Select	c.891-6713G>A		intron	N/A	ENSP00000307272.3	Q8N122-1
	RPTOR	ENST00000570891.5	TSL:1	c.891-6713G>A		intron	N/A	ENSP00000460136.1	Q8N122-2
	RPTOR	ENST00000575542.5	TSL:1	n.378-6713G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30750 AN: 152158 Hom.: 3676 Cov.: 33

Gnomad AFR AF: 0.0750

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.208

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

GnomAD4 genome AF: 0.202 AC: 30758 AN: 152276 Hom.: 3679 Cov.: 33 AF XY: 0.205 AC XY: 15261 AN XY: 74454

African (AFR) AF: 0.0752 AC: 3126 AN: 41576

American (AMR) AF: 0.170 AC: 2603 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 823 AN: 3472

East Asian (EAS) AF: 0.297 AC: 1538 AN: 5174

South Asian (SAS) AF: 0.262 AC: 1265 AN: 4830

European-Finnish (FIN) AF: 0.301 AC: 3189 AN: 10594

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.257 AC: 17465 AN: 68012

Other (OTH) AF: 0.206 AC: 434 AN: 2110

Alfa AF: 0.229 Hom.: 9540

Bravo AF: 0.185

Asia WGS AF: 0.222 AC: 770 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.1
DANN	Benign	0.49
PhyloP100		-0.87
Mutation Taster		=99/1	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2048753;

hg19: chr17-78789288;