17-80691605-C-T

Position:

• chr17-80691605-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000306801.8(RPTOR):​c.349-16236C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 152,050 control chromosomes in the GnomAD database, including 13,265 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 0.41 (13265 hom., cov: 32)
• Consequence: RPTOR ENST00000306801.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.17

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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPTOR	NM_020761.3	c.349-16236C>T		intron_variant		ENST00000306801.8	NP_065812.1
RPTOR	NM_001163034.2	c.349-16236C>T		intron_variant			NP_001156506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPTOR	ENST00000306801.8	c.349-16236C>T		intron_variant		1	NM_020761.3	ENSP00000307272	P1

Frequencies

GnomAD3 genomes AF: 0.409 AC: 62101 AN: 151932 Hom.: 13267 Cov.: 32

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.358

Gnomad ASJ AF: 0.495

Gnomad EAS AF: 0.569

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.495

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.460

Gnomad OTH AF: 0.439

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

GnomAD4 genome AF: 0.408 AC: 62106 AN: 152050 Hom.: 13265 Cov.: 32 AF XY: 0.410 AC XY: 30480 AN XY: 74324

Gnomad4 AFR AF: 0.290

Gnomad4 AMR AF: 0.357

Gnomad4 ASJ AF: 0.495

Gnomad4 EAS AF: 0.569

Gnomad4 SAS AF: 0.431

Gnomad4 FIN AF: 0.495

Gnomad4 NFE AF: 0.460

Gnomad4 OTH AF: 0.439

Alfa AF: 0.441 Hom.: 19468

Bravo AF: 0.392

Asia WGS AF: 0.437 AC: 1523 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	0.061
DANN	Benign	0.65

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: rs9906827; hg19: chr17-78665405;