rs7208536

Positions:

• chr17-80775986-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.831-15464C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 151,952 control chromosomes in the GnomAD database, including 5,783 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 0.27 (5783 hom., cov: 32)
• Consequence: RPTOR NM_020761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPTOR	NM_020761.3	c.831-15464C>T		intron_variant		ENST00000306801.8
RPTOR	NM_001163034.2	c.831-15464C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPTOR	ENST00000306801.8	c.831-15464C>T		intron_variant		1	NM_020761.3	P1

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41299 AN: 151834 Hom.: 5782 Cov.: 32

Gnomad AFR AF: 0.326

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.270

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

GnomAD4 genome AF: 0.272 AC: 41333 AN: 151952 Hom.: 5783 Cov.: 32 AF XY: 0.272 AC XY: 20186 AN XY: 74258

Gnomad4 AFR AF: 0.326

Gnomad4 AMR AF: 0.219

Gnomad4 ASJ AF: 0.302

Gnomad4 EAS AF: 0.199

Gnomad4 SAS AF: 0.275

Gnomad4 FIN AF: 0.293

Gnomad4 NFE AF: 0.253

Gnomad4 OTH AF: 0.271

Alfa AF: 0.259 Hom.: 2407

Bravo AF: 0.269

Asia WGS AF: 0.250 AC: 869 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.25
DANN	Benign	0.26

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: rs7208536; hg19: chr17-78749786;