rs7503807

Variant names:

• chr17-80617311-A-C
• rs7503807
• NM_020761.3:c.163-8380A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020761.3(RPTOR):​c.163-8380A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 152,070 control chromosomes in the GnomAD database, including 13,786 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 0.42 (13786 hom., cov: 33)
• Consequence: RPTOR NM_020761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0330
• Publications: 37 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 = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPTOR	NM_020761.3	c.163-8380A>C		intron_variant	Intron 1 of 33	ENST00000306801.8	NP_065812.1
RPTOR	NM_001163034.2	c.163-8380A>C		intron_variant	Intron 1 of 29		NP_001156506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPTOR	ENST00000306801.8	c.163-8380A>C		intron_variant	Intron 1 of 33	1	NM_020761.3	ENSP00000307272.3

Frequencies

GnomAD3 genomes AF: 0.422 AC: 64142 AN: 151950 Hom.: 13772 Cov.: 33

Gnomad AFR AF: 0.477

Gnomad AMI AF: 0.410

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.440

Gnomad OTH AF: 0.409

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

GnomAD4 genome AF: 0.422 AC: 64185 AN: 152070 Hom.: 13786 Cov.: 33 AF XY: 0.412 AC XY: 30660 AN XY: 74350

African (AFR) AF: 0.477 AC: 19783 AN: 41470

American (AMR) AF: 0.351 AC: 5361 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.360 AC: 1248 AN: 3468

East Asian (EAS) AF: 0.318 AC: 1643 AN: 5166

South Asian (SAS) AF: 0.303 AC: 1459 AN: 4818

European-Finnish (FIN) AF: 0.327 AC: 3456 AN: 10578

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.440 AC: 29898 AN: 67970

Other (OTH) AF: 0.403 AC: 852 AN: 2112

Alfa AF: 0.430 Hom.: 43449

Bravo AF: 0.423

Asia WGS AF: 0.277 AC: 968 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	3.3
DANN	Benign	0.54
PhyloP100		-0.033
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: rs7503807; hg19: chr17-78591111;