rs9900506

Positions:

• chr17-80648576-G-A
• chr17-80648576-G-C

Variant summary

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

The ENST00000306801.8(RPTOR):​c.348+4766G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.59 in 151,758 control chromosomes in the GnomAD database, including 27,049 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 0.59 (27049 hom., cov: 30)
• Consequence: RPTOR ENST00000306801.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0160

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.72 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPTOR	NM_020761.3	c.348+4766G>A		intron_variant		ENST00000306801.8	NP_065812.1
RPTOR	NM_001163034.2	c.348+4766G>A		intron_variant			NP_001156506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPTOR	ENST00000306801.8	c.348+4766G>A		intron_variant		1	NM_020761.3	ENSP00000307272	P1

Frequencies

GnomAD3 genomes AF: 0.590 AC: 89463 AN: 151640 Hom.: 27019 Cov.: 30

Gnomad AFR AF: 0.727

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.597

Gnomad EAS AF: 0.578

Gnomad SAS AF: 0.516

Gnomad FIN AF: 0.557

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.550

Gnomad OTH AF: 0.581

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

GnomAD4 genome AF: 0.590 AC: 89532 AN: 151758 Hom.: 27049 Cov.: 30 AF XY: 0.586 AC XY: 43440 AN XY: 74150

Gnomad4 AFR AF: 0.727

Gnomad4 AMR AF: 0.454

Gnomad4 ASJ AF: 0.597

Gnomad4 EAS AF: 0.577

Gnomad4 SAS AF: 0.517

Gnomad4 FIN AF: 0.557

Gnomad4 NFE AF: 0.549

Gnomad4 OTH AF: 0.579

Alfa AF: 0.555 Hom.: 47948

Bravo AF: 0.588

Asia WGS AF: 0.522 AC: 1816 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.9
DANN	Benign	0.70
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: rs9900506; hg19: chr17-78622376;