chr17-80545369-G-A

Position:

• chr17-80545369-G-A

Variant summary

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

The NM_020761.3(RPTOR):​c.-261G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 352,010 control chromosomes in the GnomAD database, including 6,889 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 0.16 (2352 hom., cov: 32)
  • Exomes 𝑓: 0.20 (4537 hom.)
• Consequence: RPTOR NM_020761.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.780

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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPTOR	NM_020761.3	c.-261G>A		5_prime_UTR_variant	1/34	ENST00000306801.8	NP_065812.1
RPTOR	NM_001163034.2	c.-261G>A		5_prime_UTR_variant	1/30		NP_001156506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPTOR	ENST00000306801	c.-261G>A		5_prime_UTR_variant	1/34	1	NM_020761.3	ENSP00000307272.3

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25053 AN: 152068 Hom.: 2351 Cov.: 32

Gnomad AFR AF: 0.0630

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.179

GnomAD4 exome AF: 0.204 AC: 40675 AN: 199824 Hom.: 4537 Cov.: 0 AF XY: 0.203 AC XY: 20608 AN XY: 101618

Gnomad4 AFR exome AF: 0.0662

Gnomad4 AMR exome AF: 0.155

Gnomad4 ASJ exome AF: 0.181

Gnomad4 EAS exome AF: 0.320

Gnomad4 SAS exome AF: 0.178

Gnomad4 FIN exome AF: 0.195

Gnomad4 NFE exome AF: 0.204

Gnomad4 OTH exome AF: 0.179

GnomAD4 genome AF: 0.165 AC: 25062 AN: 152186 Hom.: 2352 Cov.: 32 AF XY: 0.165 AC XY: 12285 AN XY: 74388

Gnomad4 AFR AF: 0.0634

Gnomad4 AMR AF: 0.174

Gnomad4 ASJ AF: 0.185

Gnomad4 EAS AF: 0.275

Gnomad4 SAS AF: 0.191

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.210

Gnomad4 OTH AF: 0.176

Alfa AF: 0.198 Hom.: 5190

Bravo AF: 0.159

Asia WGS AF: 0.176 AC: 615 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	11
DANN	Benign	0.86
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs12602885; hg19: chr17-78519169; COSMIC: COSV60817980; COSMIC: COSV60817980;