rs2589143

Variant names:

• chr17-80836887-T-G
• rs2589143
• NM_020761.3:c.1137-1035T>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.1137-1035T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.787 in 152,034 control chromosomes in the GnomAD database, including 47,390 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 0.79 (47390 hom., cov: 31)
• Consequence: RPTOR NM_020761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.412
• Publications: 6 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.845 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPTOR	NM_020761.3	c.1137-1035T>G		intron_variant	Intron 9 of 33	ENST00000306801.8	NP_065812.1
RPTOR	NM_001163034.2	c.1137-1035T>G		intron_variant	Intron 9 of 29		NP_001156506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPTOR	ENST00000306801.8	c.1137-1035T>G		intron_variant	Intron 9 of 33	1	NM_020761.3	ENSP00000307272.3

Frequencies

GnomAD3 genomes AF: 0.787 AC: 119583 AN: 151916 Hom.: 47353 Cov.: 31

Gnomad AFR AF: 0.852

Gnomad AMI AF: 0.707

Gnomad AMR AF: 0.748

Gnomad ASJ AF: 0.720

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.730

Gnomad FIN AF: 0.755

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.788

Gnomad OTH AF: 0.778

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

GnomAD4 genome AF: 0.787 AC: 119671 AN: 152034 Hom.: 47390 Cov.: 31 AF XY: 0.782 AC XY: 58073 AN XY: 74302

African (AFR) AF: 0.852 AC: 35344 AN: 41474

American (AMR) AF: 0.747 AC: 11433 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.720 AC: 2499 AN: 3472

East Asian (EAS) AF: 0.554 AC: 2847 AN: 5142

South Asian (SAS) AF: 0.729 AC: 3511 AN: 4814

European-Finnish (FIN) AF: 0.755 AC: 7990 AN: 10582

Middle Eastern (MID) AF: 0.796 AC: 234 AN: 294

European-Non Finnish (NFE) AF: 0.788 AC: 53524 AN: 67942

Other (OTH) AF: 0.781 AC: 1646 AN: 2108

Alfa AF: 0.786 Hom.: 30756

Bravo AF: 0.790

Asia WGS AF: 0.698 AC: 2431 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	1.4
DANN	Benign	0.67
PhyloP100		0.41
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: rs2589143; hg19: chr17-78810687;