chr17-80553494-G-A

Variant names:

• chr17-80553494-G-A
• rs7209040
• NM_020761.3:c.162+7703G>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.162+7703G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 152,038 control chromosomes in the GnomAD database, including 15,129 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 0.44 (15129 hom., cov: 33)
• Consequence: RPTOR NM_020761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.52
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPTOR	NM_020761.3	c.162+7703G>A		intron_variant	Intron 1 of 33	ENST00000306801.8	NP_065812.1
RPTOR	NM_001163034.2	c.162+7703G>A		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.162+7703G>A		intron_variant	Intron 1 of 33	1	NM_020761.3	ENSP00000307272.3

Frequencies

GnomAD3 genomes AF: 0.442 AC: 67151 AN: 151918 Hom.: 15125 Cov.: 33

Gnomad AFR AF: 0.400

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.510

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.475

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

GnomAD4 genome AF: 0.442 AC: 67153 AN: 152038 Hom.: 15129 Cov.: 33 AF XY: 0.436 AC XY: 32424 AN XY: 74300

African (AFR) AF: 0.399 AC: 16556 AN: 41460

American (AMR) AF: 0.364 AC: 5559 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.554 AC: 1922 AN: 3472

East Asian (EAS) AF: 0.301 AC: 1557 AN: 5174

South Asian (SAS) AF: 0.338 AC: 1628 AN: 4822

European-Finnish (FIN) AF: 0.453 AC: 4784 AN: 10550

Middle Eastern (MID) AF: 0.507 AC: 148 AN: 292

European-Non Finnish (NFE) AF: 0.494 AC: 33593 AN: 67958

Other (OTH) AF: 0.474 AC: 1000 AN: 2108

Alfa AF: 0.471 Hom.: 48349

Bravo AF: 0.434

Asia WGS AF: 0.348 AC: 1212 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.3
DANN	Benign	0.71
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs7209040; hg19: chr17-78527294;