rs7502563

Positions:

• chr17-80947993-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.3265+642G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 152,150 control chromosomes in the GnomAD database, including 10,039 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 (10039 hom., cov: 33)
• Consequence: RPTOR NM_020761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.435

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPTOR	NM_020761.3	c.3265+642G>A		intron_variant		ENST00000306801.8
RPTOR	NM_001163034.2	c.2791+642G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPTOR	ENST00000306801.8	c.3265+642G>A		intron_variant		1	NM_020761.3	P1

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51915 AN: 152034 Hom.: 10032 Cov.: 33

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.551

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.378

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

GnomAD4 genome AF: 0.341 AC: 51945 AN: 152150 Hom.: 10039 Cov.: 33 AF XY: 0.342 AC XY: 25462 AN XY: 74376

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.394

Gnomad4 ASJ AF: 0.417

Gnomad4 EAS AF: 0.552

Gnomad4 SAS AF: 0.348

Gnomad4 FIN AF: 0.405

Gnomad4 NFE AF: 0.410

Gnomad4 OTH AF: 0.379

Alfa AF: 0.364 Hom.: 2422

Bravo AF: 0.333

Asia WGS AF: 0.419 AC: 1458 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.9
DANN	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs7502563; hg19: chr17-78921793;