rs12946049

Positions:

• chr17-80620869-T-C

Variant summary

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

The NM_020761.3(RPTOR):​c.163-4822T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 152,266 control chromosomes in the GnomAD database, including 3,008 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 0.18 (3008 hom., cov: 33)
• Consequence: RPTOR NM_020761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.124

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPTOR	NM_020761.3	c.163-4822T>C		intron_variant		ENST00000306801.8
RPTOR	NM_001163034.2	c.163-4822T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPTOR	ENST00000306801.8	c.163-4822T>C		intron_variant		1	NM_020761.3	P1

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28152 AN: 152146 Hom.: 3010 Cov.: 33

Gnomad AFR AF: 0.0702

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.204

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.203

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

GnomAD4 genome AF: 0.185 AC: 28144 AN: 152266 Hom.: 3008 Cov.: 33 AF XY: 0.184 AC XY: 13718 AN XY: 74462

Gnomad4 AFR AF: 0.0701

Gnomad4 AMR AF: 0.189

Gnomad4 ASJ AF: 0.203

Gnomad4 EAS AF: 0.280

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.205

Gnomad4 NFE AF: 0.241

Gnomad4 OTH AF: 0.200

Alfa AF: 0.194 Hom.: 471

Bravo AF: 0.177

Asia WGS AF: 0.182 AC: 635 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.3
DANN	Benign	0.28

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: rs12946049; hg19: chr17-78594669;