rs3817293

Variant names:

• chr17-80925795-G-A
• rs3817293
• NM_020761.3:c.2919+315G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RPTOR	NM_020761.3	c.2919+315G>A		intron_variant	Intron 24 of 33	ENST00000306801.8	NP_065812.1
RPTOR	NM_001163034.2	c.2445+315G>A		intron_variant	Intron 20 of 29		NP_001156506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPTOR	ENST00000306801.8	c.2919+315G>A		intron_variant	Intron 24 of 33	1	NM_020761.3	ENSP00000307272.3
RPTOR	ENST00000575542.5	n.2406+315G>A		intron_variant	Intron 20 of 29	1
RPTOR	ENST00000697423.1	c.2973+315G>A		intron_variant	Intron 24 of 33			ENSP00000513305.1
RPTOR	ENST00000544334.6	c.2445+315G>A		intron_variant	Intron 20 of 29	5		ENSP00000442479.2

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

African (AFR) AF: 0.357 AC: 14794 AN: 41492

American (AMR) AF: 0.239 AC: 3653 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 513 AN: 3470

East Asian (EAS) AF: 0.0924 AC: 478 AN: 5174

South Asian (SAS) AF: 0.110 AC: 533 AN: 4828

European-Finnish (FIN) AF: 0.246 AC: 2613 AN: 10606

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.209 AC: 14219 AN: 67986

Other (OTH) AF: 0.221 AC: 467 AN: 2112

Alfa AF: 0.231 Hom.: 1889

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
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3817293; hg19: chr17-78899595;