rs6565497

Positions:

• chr17-80938833-A-T

Variant summary

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

The NM_020761.3(RPTOR):​c.2920-1663A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.605 in 152,184 control chromosomes in the GnomAD database, including 28,607 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 0.61 (28607 hom., cov: 33)
• Consequence: RPTOR NM_020761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0610

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.741 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPTOR	NM_020761.3	c.2920-1663A>T		intron_variant		ENST00000306801.8	NP_065812.1
RPTOR	NM_001163034.2	c.2446-1663A>T		intron_variant			NP_001156506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPTOR	ENST00000306801.8	c.2920-1663A>T		intron_variant		1	NM_020761.3	ENSP00000307272	P1
RPTOR	ENST00000575542.5	n.2407-1663A>T		intron_variant, non_coding_transcript_variant		1
RPTOR	ENST00000544334.6	c.2446-1663A>T		intron_variant		5		ENSP00000442479
RPTOR	ENST00000697423.1	c.2974-1663A>T		intron_variant				ENSP00000513305

Frequencies

GnomAD3 genomes AF: 0.605 AC: 92004 AN: 152066 Hom.: 28567 Cov.: 33

Gnomad AFR AF: 0.749

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.583

Gnomad ASJ AF: 0.460

Gnomad EAS AF: 0.572

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.518

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.559

Gnomad OTH AF: 0.572

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

GnomAD4 genome AF: 0.605 AC: 92101 AN: 152184 Hom.: 28607 Cov.: 33 AF XY: 0.598 AC XY: 44486 AN XY: 74388

Gnomad4 AFR AF: 0.748

Gnomad4 AMR AF: 0.583

Gnomad4 ASJ AF: 0.460

Gnomad4 EAS AF: 0.573

Gnomad4 SAS AF: 0.491

Gnomad4 FIN AF: 0.518

Gnomad4 NFE AF: 0.559

Gnomad4 OTH AF: 0.570

Alfa AF: 0.582 Hom.: 3277

Bravo AF: 0.617

Asia WGS AF: 0.536 AC: 1863 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.6
DANN	Benign	0.86

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: rs6565497; hg19: chr17-78912633;