rs2672890

Positions:

• chr17-80860407-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.1509+2507C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 152,152 control chromosomes in the GnomAD database, including 2,707 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 0.17 (2707 hom., cov: 32)
• Consequence: RPTOR NM_020761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.367

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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPTOR	NM_020761.3	c.1509+2507C>T		intron_variant		ENST00000306801.8	NP_065812.1
RPTOR	NM_001163034.2	c.1509+2507C>T		intron_variant			NP_001156506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPTOR	ENST00000306801.8	c.1509+2507C>T		intron_variant		1	NM_020761.3	ENSP00000307272	P1

Frequencies

GnomAD3 genomes AF: 0.171 AC: 26003 AN: 152034 Hom.: 2703 Cov.: 32

Gnomad AFR AF: 0.0689

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.362

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.162

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

GnomAD4 genome AF: 0.171 AC: 26002 AN: 152152 Hom.: 2707 Cov.: 32 AF XY: 0.177 AC XY: 13169 AN XY: 74368

Gnomad4 AFR AF: 0.0687

Gnomad4 AMR AF: 0.262

Gnomad4 ASJ AF: 0.127

Gnomad4 EAS AF: 0.362

Gnomad4 SAS AF: 0.292

Gnomad4 FIN AF: 0.219

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.166

Alfa AF: 0.186 Hom.: 3841

Bravo AF: 0.170

Asia WGS AF: 0.330 AC: 1144 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.3
DANN	Benign	0.95

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: rs2672890; hg19: chr17-78834207; COSMIC: COSV60805520; COSMIC: COSV60805520;