rs3817293

Positions:

• chr17-80925795-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.2919+315G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 152,162 control chromosomes in the GnomAD database, including 5,079 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 0.25 (5079 hom., cov: 33)
• Consequence: RPTOR NM_020761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.79

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPTOR	NM_020761.3	c.2919+315G>A		intron_variant		ENST00000306801.8	NP_065812.1
RPTOR	NM_001163034.2	c.2445+315G>A		intron_variant			NP_001156506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPTOR	ENST00000306801.8	c.2919+315G>A		intron_variant		1	NM_020761.3	ENSP00000307272	P1
RPTOR	ENST00000575542.5	n.2406+315G>A		intron_variant, non_coding_transcript_variant		1
RPTOR	ENST00000544334.6	c.2445+315G>A		intron_variant		5		ENSP00000442479
RPTOR	ENST00000697423.1	c.2973+315G>A		intron_variant				ENSP00000513305

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37397 AN: 152044 Hom.: 5058 Cov.: 33

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.142

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.0926

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.224

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

GnomAD4 genome AF: 0.246 AC: 37454 AN: 152162 Hom.: 5079 Cov.: 33 AF XY: 0.243 AC XY: 18047 AN XY: 74396

Gnomad4 AFR AF: 0.357

Gnomad4 AMR AF: 0.239

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.0924

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.246

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.221

Alfa AF: 0.231 Hom.: 1532

Bravo AF: 0.252

Asia WGS AF: 0.101 AC: 354 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.12
DANN	Benign	0.69

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: rs3817293; hg19: chr17-78899595;