17-80752461-T-C

Variant names:

• chr17-80752461-T-C
• rs4969230
• NM_020761.3:c.655-1549T>C

Variant summary

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

The NM_020761.3(RPTOR):​c.655-1549T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 152,180 control chromosomes in the GnomAD database, including 11,245 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 0.37 (11245 hom., cov: 34)
• Consequence: RPTOR NM_020761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0870
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.541 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPTOR	NM_020761.3	c.655-1549T>C		intron_variant	Intron 5 of 33	ENST00000306801.8	NP_065812.1
RPTOR	NM_001163034.2	c.655-1549T>C		intron_variant	Intron 5 of 29		NP_001156506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPTOR	ENST00000306801.8	c.655-1549T>C		intron_variant	Intron 5 of 33	1	NM_020761.3	ENSP00000307272.3

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56465 AN: 152062 Hom.: 11230 Cov.: 34

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.584

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.559

Gnomad SAS AF: 0.484

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.366

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.367

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

GnomAD4 genome AF: 0.371 AC: 56530 AN: 152180 Hom.: 11245 Cov.: 34 AF XY: 0.380 AC XY: 28259 AN XY: 74382

African (AFR) AF: 0.239 AC: 9942 AN: 41532

American (AMR) AF: 0.476 AC: 7274 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 1207 AN: 3470

East Asian (EAS) AF: 0.558 AC: 2892 AN: 5180

South Asian (SAS) AF: 0.485 AC: 2338 AN: 4822

European-Finnish (FIN) AF: 0.439 AC: 4637 AN: 10568

Middle Eastern (MID) AF: 0.356 AC: 104 AN: 292

European-Non Finnish (NFE) AF: 0.394 AC: 26821 AN: 68008

Other (OTH) AF: 0.370 AC: 782 AN: 2112

Alfa AF: 0.395 Hom.: 19560

Bravo AF: 0.372

Asia WGS AF: 0.548 AC: 1903 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.69
PhyloP100		-0.087
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: rs4969230; hg19: chr17-78726261;