chr17-80734618-A-G

Variant names:

• chr17-80734618-A-G
• rs9915378
• NM_020761.3:c.654+3912A>G

Variant summary

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

The NM_020761.3(RPTOR):​c.654+3912A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.69 in 152,144 control chromosomes in the GnomAD database, including 37,792 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 0.69 (37792 hom., cov: 32)
• Consequence: RPTOR NM_020761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.88
• Publications: 14 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=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.888 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPTOR	NM_020761.3	c.654+3912A>G		intron_variant	Intron 5 of 33	ENST00000306801.8	NP_065812.1
RPTOR	NM_001163034.2	c.654+3912A>G		intron_variant	Intron 5 of 29		NP_001156506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPTOR	ENST00000306801.8	c.654+3912A>G		intron_variant	Intron 5 of 33	1	NM_020761.3	ENSP00000307272.3

Frequencies

GnomAD3 genomes AF: 0.690 AC: 104940 AN: 152028 Hom.: 37744 Cov.: 32

Gnomad AFR AF: 0.896

Gnomad AMI AF: 0.561

Gnomad AMR AF: 0.529

Gnomad ASJ AF: 0.682

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.530

Gnomad FIN AF: 0.565

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.650

Gnomad OTH AF: 0.679

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

GnomAD4 genome AF: 0.690 AC: 105035 AN: 152144 Hom.: 37792 Cov.: 32 AF XY: 0.679 AC XY: 50466 AN XY: 74358

African (AFR) AF: 0.896 AC: 37189 AN: 41516

American (AMR) AF: 0.528 AC: 8074 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.682 AC: 2363 AN: 3464

East Asian (EAS) AF: 0.499 AC: 2584 AN: 5178

South Asian (SAS) AF: 0.530 AC: 2552 AN: 4814

European-Finnish (FIN) AF: 0.565 AC: 5970 AN: 10570

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.650 AC: 44176 AN: 67996

Other (OTH) AF: 0.676 AC: 1427 AN: 2112

Alfa AF: 0.660 Hom.: 95173

Bravo AF: 0.694

Asia WGS AF: 0.501 AC: 1745 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.056
DANN	Benign	0.36
PhyloP100		-1.9
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: rs9915378; hg19: chr17-78708418;