rs9894401

Positions:

• chr17-80768726-G-A
• chr17-80768726-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.830+14541G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 151,886 control chromosomes in the GnomAD database, including 5,136 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 0.26 (5136 hom., cov: 32)
• Consequence: RPTOR NM_020761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05

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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPTOR	NM_020761.3	c.830+14541G>A		intron_variant		ENST00000306801.8
RPTOR	NM_001163034.2	c.830+14541G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPTOR	ENST00000306801.8	c.830+14541G>A		intron_variant		1	NM_020761.3	P1

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39201 AN: 151768 Hom.: 5138 Cov.: 32

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.272

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

GnomAD4 genome AF: 0.258 AC: 39225 AN: 151886 Hom.: 5136 Cov.: 32 AF XY: 0.260 AC XY: 19311 AN XY: 74234

Gnomad4 AFR AF: 0.251

Gnomad4 AMR AF: 0.221

Gnomad4 ASJ AF: 0.315

Gnomad4 EAS AF: 0.200

Gnomad4 SAS AF: 0.321

Gnomad4 FIN AF: 0.295

Gnomad4 NFE AF: 0.263

Gnomad4 OTH AF: 0.273

Alfa AF: 0.265 Hom.: 2491

Bravo AF: 0.250

Asia WGS AF: 0.269 AC: 935 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.14
DANN	Benign	0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs9894401; hg19: chr17-78742526;