rs4890047

chr17-80575639-C-T

Variant summary

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

The NM_020761.3(RPTOR):c.162+29848C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 152,042 control chromosomes in the GnomAD database, including 6,954 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 0.29 (6954 hom., cov: 32)
• Consequence: RPTOR NM_020761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.561

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=-1.06).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPTOR	NM_020761.3	c.162+29848C>T		intron_variant		ENST00000306801.8
LOC105371922	XR_007065932.1	n.302+4165G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPTOR	ENST00000306801.8	c.162+29848C>T		intron_variant		1	NM_020761.3	P1

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44707 AN: 151924 Hom.: 6932 Cov.: 32

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.263

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

GnomAD4 genome AF: 0.294 AC: 44769 AN: 152042 Hom.: 6954 Cov.: 32 AF XY: 0.301 AC XY: 22390 AN XY: 74340

Gnomad4 AFR AF: 0.285

Gnomad4 AMR AF: 0.411

Gnomad4 ASJ AF: 0.204

Gnomad4 EAS AF: 0.419

Gnomad4 SAS AF: 0.383

Gnomad4 FIN AF: 0.345

Gnomad4 NFE AF: 0.256

Gnomad4 OTH AF: 0.267

Alfa AF: 0.292 Hom.: 1141

Bravo AF: 0.301

Asia WGS AF: 0.414 AC: 1435 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
Cadd	Benign	2.1
Dann	Benign	0.82

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: rs4890047; hg19: chr17-78549439;