rs6565497

Variant names:

• chr17-80938833-A-T
• rs6565497
• NM_020761.3:c.2920-1663A>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RPTOR	NM_020761.3	c.2920-1663A>T		intron_variant	Intron 24 of 33	ENST00000306801.8	NP_065812.1
RPTOR	NM_001163034.2	c.2446-1663A>T		intron_variant	Intron 20 of 29		NP_001156506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPTOR	ENST00000306801.8	c.2920-1663A>T		intron_variant	Intron 24 of 33	1	NM_020761.3	ENSP00000307272.3
RPTOR	ENST00000575542.5	n.2407-1663A>T		intron_variant	Intron 20 of 29	1
RPTOR	ENST00000697423.1	c.2974-1663A>T		intron_variant	Intron 24 of 33			ENSP00000513305.1
RPTOR	ENST00000544334.6	c.2446-1663A>T		intron_variant	Intron 20 of 29	5		ENSP00000442479.2

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

African (AFR) AF: 0.748 AC: 31064 AN: 41504

American (AMR) AF: 0.583 AC: 8912 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 1596 AN: 3472

East Asian (EAS) AF: 0.573 AC: 2964 AN: 5174

South Asian (SAS) AF: 0.491 AC: 2370 AN: 4826

European-Finnish (FIN) AF: 0.518 AC: 5489 AN: 10594

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.559 AC: 37985 AN: 68010

Other (OTH) AF: 0.570 AC: 1205 AN: 2114

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
PhyloP100		-0.061
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6565497; hg19: chr17-78912633;