rs7209040

chr17-80553494-G-Achr17-80553494-G-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.87).
• 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/exons	MANE	UniProt
RPTOR	NM_020761.3	c.162+7703G>A		intron_variant		ENST00000306801.8
RPTOR	NM_001163034.2	c.162+7703G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPTOR	ENST00000306801.8	c.162+7703G>A		intron_variant		1	NM_020761.3	P1

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

Gnomad4 AFR AF: 0.399

Gnomad4 AMR AF: 0.364

Gnomad4 ASJ AF: 0.554

Gnomad4 EAS AF: 0.301

Gnomad4 SAS AF: 0.338

Gnomad4 FIN AF: 0.453

Gnomad4 NFE AF: 0.494

Gnomad4 OTH AF: 0.474

Alfa AF: 0.479 Hom.: 33878

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs7209040; hg19: chr17-78527294;