NM_020761.3:c.348+4766G>A

Variant names:

• chr17-80648576-G-A
• rs9900506
• NM_020761.3:c.348+4766G>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.348+4766G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.59 in 151,758 control chromosomes in the GnomAD database, including 27,049 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 0.59 (27049 hom., cov: 30)
• Consequence: RPTOR NM_020761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0160
• Publications: 12 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.72 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPTOR	NM_020761.3	c.348+4766G>A		intron_variant	Intron 3 of 33	ENST00000306801.8	NP_065812.1
RPTOR	NM_001163034.2	c.348+4766G>A		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.348+4766G>A		intron_variant	Intron 3 of 33	1	NM_020761.3	ENSP00000307272.3

Frequencies

GnomAD3 genomes AF: 0.590 AC: 89463 AN: 151640 Hom.: 27019 Cov.: 30

Gnomad AFR AF: 0.727

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.597

Gnomad EAS AF: 0.578

Gnomad SAS AF: 0.516

Gnomad FIN AF: 0.557

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.550

Gnomad OTH AF: 0.581

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

GnomAD4 genome AF: 0.590 AC: 89532 AN: 151758 Hom.: 27049 Cov.: 30 AF XY: 0.586 AC XY: 43440 AN XY: 74150

African (AFR) AF: 0.727 AC: 30051 AN: 41348

American (AMR) AF: 0.454 AC: 6933 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.597 AC: 2073 AN: 3470

East Asian (EAS) AF: 0.577 AC: 2970 AN: 5148

South Asian (SAS) AF: 0.517 AC: 2489 AN: 4814

European-Finnish (FIN) AF: 0.557 AC: 5854 AN: 10508

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.549 AC: 37310 AN: 67902

Other (OTH) AF: 0.579 AC: 1221 AN: 2108

Alfa AF: 0.561 Hom.: 77473

Bravo AF: 0.588

Asia WGS AF: 0.522 AC: 1816 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.9
DANN	Benign	0.70
PhyloP100		-0.016
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs9900506; hg19: chr17-78622376;