rs35544492

Positions:

• chr17-80681576-T-A
• chr17-80681576-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020761.3(RPTOR):​c.349-26265T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 139,754 control chromosomes in the GnomAD database, including 2,751 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 0.13 (2751 hom., cov: 26)
• Consequence: RPTOR NM_020761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0760

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPTOR	NM_020761.3	c.349-26265T>A		intron_variant		ENST00000306801.8	NP_065812.1
RPTOR	NM_001163034.2	c.349-26265T>A		intron_variant			NP_001156506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPTOR	ENST00000306801.8	c.349-26265T>A		intron_variant		1	NM_020761.3	ENSP00000307272	P1

Frequencies

GnomAD3 genomes AF: 0.134 AC: 18721 AN: 139644 Hom.: 2747 Cov.: 26

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.0430

Gnomad AMR AF: 0.0847

Gnomad ASJ AF: 0.0852

Gnomad EAS AF: 0.00237

Gnomad SAS AF: 0.0182

Gnomad FIN AF: 0.0391

Gnomad MID AF: 0.105

Gnomad NFE AF: 0.0847

Gnomad OTH AF: 0.127

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

GnomAD4 genome AF: 0.134 AC: 18744 AN: 139754 Hom.: 2751 Cov.: 26 AF XY: 0.127 AC XY: 8716 AN XY: 68422

Gnomad4 AFR AF: 0.311

Gnomad4 AMR AF: 0.0846

Gnomad4 ASJ AF: 0.0852

Gnomad4 EAS AF: 0.00238

Gnomad4 SAS AF: 0.0179

Gnomad4 FIN AF: 0.0391

Gnomad4 NFE AF: 0.0847

Gnomad4 OTH AF: 0.125

Alfa AF: 0.0287 Hom.: 19

Bravo AF: 0.171

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.69
DANN	Benign	0.71

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

Publications

LitVar

Other links and lift over

dbSNP: rs35544492; hg19: chr17-78655376;