17-80946120-C-T

Position:

• chr17-80946120-C-T

Variant summary

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

The ENST00000306801.8(RPTOR):​c.3140+339C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 151,930 control chromosomes in the GnomAD database, including 20,889 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 0.52 (20889 hom., cov: 32)
• Consequence: RPTOR ENST00000306801.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPTOR	NM_020761.3	c.3140+339C>T		intron_variant		ENST00000306801.8	NP_065812.1
RPTOR	NM_001163034.2	c.2666+339C>T		intron_variant			NP_001156506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPTOR	ENST00000306801.8	c.3140+339C>T		intron_variant		1	NM_020761.3	ENSP00000307272	P1

Frequencies

GnomAD3 genomes AF: 0.520 AC: 78985 AN: 151812 Hom.: 20865 Cov.: 32

Gnomad AFR AF: 0.555

Gnomad AMI AF: 0.685

Gnomad AMR AF: 0.546

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.291

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.559

Gnomad MID AF: 0.561

Gnomad NFE AF: 0.511

Gnomad OTH AF: 0.505

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

GnomAD4 genome AF: 0.520 AC: 79047 AN: 151930 Hom.: 20889 Cov.: 32 AF XY: 0.519 AC XY: 38494 AN XY: 74234

Gnomad4 AFR AF: 0.555

Gnomad4 AMR AF: 0.546

Gnomad4 ASJ AF: 0.531

Gnomad4 EAS AF: 0.290

Gnomad4 SAS AF: 0.397

Gnomad4 FIN AF: 0.559

Gnomad4 NFE AF: 0.511

Gnomad4 OTH AF: 0.500

Alfa AF: 0.503 Hom.: 10244

Bravo AF: 0.524

Asia WGS AF: 0.320 AC: 1113 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.49
DANN	Benign	0.73

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: rs2271612; hg19: chr17-78919920;