17-80584457-C-G

Position:

• chr17-80584457-C-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000306801.8(RPTOR):​c.162+38666C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00224 in 140,350 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0022 (0 hom., cov: 28)
• Consequence: RPTOR ENST00000306801.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.396

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BS2: High AC in GnomAd4 at 315 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPTOR	NM_020761.3	c.162+38666C>G		intron_variant		ENST00000306801.8	NP_065812.1
LOC105371922	XR_007065932.1	n.138+2367G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPTOR	ENST00000306801.8	c.162+38666C>G		intron_variant		1	NM_020761.3	ENSP00000307272	P1

Frequencies

GnomAD3 genomes AF: 0.00225 AC: 315 AN: 140236 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.00282

Gnomad AMI AF: 0.00113

Gnomad AMR AF: 0.00210

Gnomad ASJ AF: 0.00308

Gnomad EAS AF: 0.00441

Gnomad SAS AF: 0.00325

Gnomad FIN AF: 0.00159

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00173

Gnomad OTH AF: 0.00422

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

GnomAD4 genome AF: 0.00224 AC: 315 AN: 140350 Hom.: 0 Cov.: 28 AF XY: 0.00226 AC XY: 155 AN XY: 68666

Gnomad4 AFR AF: 0.00281

Gnomad4 AMR AF: 0.00210

Gnomad4 ASJ AF: 0.00308

Gnomad4 EAS AF: 0.00442

Gnomad4 SAS AF: 0.00325

Gnomad4 FIN AF: 0.00159

Gnomad4 NFE AF: 0.00173

Gnomad4 OTH AF: 0.00417

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.5
DANN	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11655474; hg19: chr17-78558257;