rs12951309

Positions:

• chr17-80584486-G-A

Variant summary

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

The ENST00000306801.8(RPTOR):​c.162+38695G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 152,022 control chromosomes in the GnomAD database, including 3,001 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 0.19 (3001 hom., cov: 31)
• Consequence: RPTOR ENST00000306801.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.10

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]

LOC105371922 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPTOR	NM_020761.3	c.162+38695G>A		intron_variant		ENST00000306801.8	NP_065812.1
LOC105371922	XR_007065932.1	n.138+2338C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPTOR	ENST00000306801.8	c.162+38695G>A		intron_variant		1	NM_020761.3	ENSP00000307272	P1

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28627 AN: 151904 Hom.: 3000 Cov.: 31

Gnomad AFR AF: 0.0877

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.205

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

GnomAD4 genome AF: 0.188 AC: 28635 AN: 152022 Hom.: 3001 Cov.: 31 AF XY: 0.187 AC XY: 13918 AN XY: 74288

Gnomad4 AFR AF: 0.0880

Gnomad4 AMR AF: 0.192

Gnomad4 ASJ AF: 0.203

Gnomad4 EAS AF: 0.276

Gnomad4 SAS AF: 0.196

Gnomad4 FIN AF: 0.200

Gnomad4 NFE AF: 0.238

Gnomad4 OTH AF: 0.202

Alfa AF: 0.229 Hom.: 8591

Bravo AF: 0.182

Asia WGS AF: 0.182 AC: 637 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	0.0040
DANN	Benign	0.68

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: rs12951309; hg19: chr17-78558286;