17-80584457-C-T

Variant names:

• chr17-80584457-C-T
• rs11655474
• NM_020761.3:c.162+38666C>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.162+38666C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 143,996 control chromosomes in the GnomAD database, including 6,021 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 0.30 (6021 hom., cov: 28)
• Consequence: RPTOR NM_020761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.396
• Publications: 5 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]

LOC105371922 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020761.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPTOR	NM_020761.3	MANE Select	c.162+38666C>T		intron	N/A	NP_065812.1
	RPTOR	NM_001163034.2		c.162+38666C>T		intron	N/A	NP_001156506.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPTOR	ENST00000306801.8	TSL:1 MANE Select	c.162+38666C>T		intron	N/A	ENSP00000307272.3
	RPTOR	ENST00000570891.5	TSL:1	c.162+38666C>T		intron	N/A	ENSP00000460136.1
	RPTOR	ENST00000697423.1		c.216+38666C>T		intron	N/A	ENSP00000513305.1

Frequencies

GnomAD3 genomes AF: 0.303 AC: 43590 AN: 143880 Hom.: 6018 Cov.: 28

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.382

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.325

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

GnomAD4 genome AF: 0.303 AC: 43587 AN: 143996 Hom.: 6021 Cov.: 28 AF XY: 0.304 AC XY: 21360 AN XY: 70208

African (AFR) AF: 0.296 AC: 11520 AN: 38858

American (AMR) AF: 0.246 AC: 3508 AN: 14238

Ashkenazi Jewish (ASJ) AF: 0.404 AC: 1363 AN: 3370

East Asian (EAS) AF: 0.276 AC: 1350 AN: 4892

South Asian (SAS) AF: 0.285 AC: 1250 AN: 4388

European-Finnish (FIN) AF: 0.345 AC: 3492 AN: 10116

Middle Eastern (MID) AF: 0.376 AC: 106 AN: 282

European-Non Finnish (NFE) AF: 0.310 AC: 20126 AN: 64970

Other (OTH) AF: 0.327 AC: 651 AN: 1992

Alfa AF: 0.292 Hom.: 868

Bravo AF: 0.287

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.5
DANN	Benign	0.77
PhyloP100		0.40
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: rs11655474; hg19: chr17-78558257;