17-80909040-A-G

Position:

• chr17-80909040-A-G

Variant summary

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

The NM_020761.3(RPTOR):​c.2520+111A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 740,206 control chromosomes in the GnomAD database, including 43,833 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 0.34 (9213 hom., cov: 33)
  • Exomes 𝑓: 0.34 (34620 hom.)
• Consequence: RPTOR NM_020761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0170

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]

RPTOR (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPTOR	NM_020761.3	c.2520+111A>G		intron_variant		ENST00000306801.8	NP_065812.1
RPTOR	NM_001163034.2	c.2046+111A>G		intron_variant			NP_001156506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPTOR	ENST00000306801.8	c.2520+111A>G		intron_variant		1	NM_020761.3	ENSP00000307272.3

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52172 AN: 152030 Hom.: 9206 Cov.: 33

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.476

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.325

GnomAD4 exome AF: 0.339 AC: 199315 AN: 588058 Hom.: 34620 AF XY: 0.339 AC XY: 106641 AN XY: 314746

Gnomad4 AFR exome AF: 0.395

Gnomad4 AMR exome AF: 0.313

Gnomad4 ASJ exome AF: 0.316

Gnomad4 EAS exome AF: 0.488

Gnomad4 SAS exome AF: 0.353

Gnomad4 FIN exome AF: 0.270

Gnomad4 NFE exome AF: 0.331

Gnomad4 OTH exome AF: 0.341

GnomAD4 genome AF: 0.343 AC: 52203 AN: 152148 Hom.: 9213 Cov.: 33 AF XY: 0.339 AC XY: 25237 AN XY: 74378

Gnomad4 AFR AF: 0.394

Gnomad4 AMR AF: 0.322

Gnomad4 ASJ AF: 0.301

Gnomad4 EAS AF: 0.477

Gnomad4 SAS AF: 0.344

Gnomad4 FIN AF: 0.249

Gnomad4 NFE AF: 0.325

Gnomad4 OTH AF: 0.326

Alfa AF: 0.321 Hom.: 7732

Bravo AF: 0.351

Asia WGS AF: 0.421 AC: 1462 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.17
DANN	Benign	0.36

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: rs1468030; hg19: chr17-78882840; COSMIC: COSV60806382;