rs7208502

Variant names:

• chr17-80696528-C-T
• rs7208502
• NM_020761.3:c.349-11313C>T

Variant summary

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

The NM_020761.3(RPTOR):​c.349-11313C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 152,020 control chromosomes in the GnomAD database, including 13,255 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 0.41 (13255 hom., cov: 33)
• Consequence: RPTOR NM_020761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.224
• Publications: 8 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPTOR	NM_020761.3	c.349-11313C>T		intron_variant	Intron 3 of 33	ENST00000306801.8	NP_065812.1
RPTOR	NM_001163034.2	c.349-11313C>T		intron_variant	Intron 3 of 29		NP_001156506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPTOR	ENST00000306801.8	c.349-11313C>T		intron_variant	Intron 3 of 33	1	NM_020761.3	ENSP00000307272.3

Frequencies

GnomAD3 genomes AF: 0.409 AC: 62098 AN: 151902 Hom.: 13257 Cov.: 33

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.357

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.570

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.496

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.460

Gnomad OTH AF: 0.439

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

GnomAD4 genome AF: 0.409 AC: 62102 AN: 152020 Hom.: 13255 Cov.: 33 AF XY: 0.410 AC XY: 30481 AN XY: 74328

African (AFR) AF: 0.291 AC: 12062 AN: 41468

American (AMR) AF: 0.356 AC: 5438 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.497 AC: 1723 AN: 3470

East Asian (EAS) AF: 0.570 AC: 2943 AN: 5164

South Asian (SAS) AF: 0.431 AC: 2080 AN: 4822

European-Finnish (FIN) AF: 0.496 AC: 5235 AN: 10564

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.460 AC: 31251 AN: 67954

Other (OTH) AF: 0.439 AC: 922 AN: 2102

Alfa AF: 0.439 Hom.: 8404

Bravo AF: 0.392

Asia WGS AF: 0.436 AC: 1519 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.71
DANN	Benign	0.74
PhyloP100		-0.22
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: rs7208502; hg19: chr17-78670328;