rs7215564

Positions:

• chr17-80763487-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.830+9302C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.842 in 152,178 control chromosomes in the GnomAD database, including 54,606 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 0.84 (54606 hom., cov: 31)
• Consequence: RPTOR NM_020761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.994

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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPTOR	NM_020761.3	c.830+9302C>T		intron_variant		ENST00000306801.8	NP_065812.1
RPTOR	NM_001163034.2	c.830+9302C>T		intron_variant			NP_001156506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPTOR	ENST00000306801.8	c.830+9302C>T		intron_variant		1	NM_020761.3	ENSP00000307272.3

Frequencies

GnomAD3 genomes AF: 0.842 AC: 127992 AN: 152060 Hom.: 54549 Cov.: 31

Gnomad AFR AF: 0.689

Gnomad AMI AF: 0.942

Gnomad AMR AF: 0.890

Gnomad ASJ AF: 0.867

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.972

Gnomad FIN AF: 0.930

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.886

Gnomad OTH AF: 0.847

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

GnomAD4 genome AF: 0.842 AC: 128109 AN: 152178 Hom.: 54606 Cov.: 31 AF XY: 0.849 AC XY: 63175 AN XY: 74394

Gnomad4 AFR AF: 0.690

Gnomad4 AMR AF: 0.891

Gnomad4 ASJ AF: 0.867

Gnomad4 EAS AF: 0.997

Gnomad4 SAS AF: 0.973

Gnomad4 FIN AF: 0.930

Gnomad4 NFE AF: 0.886

Gnomad4 OTH AF: 0.849

Alfa AF: 0.880 Hom.: 29448

Bravo AF: 0.833

Asia WGS AF: 0.964 AC: 3351 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	0.53
DANN	Benign	0.51
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: rs7215564; hg19: chr17-78737287;