17-80860407-C-T

Variant names:

• chr17-80860407-C-T
• rs2672890
• NM_020761.3:c.1509+2507C>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.1509+2507C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 152,152 control chromosomes in the GnomAD database, including 2,707 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 0.17 (2707 hom., cov: 32)
• Consequence: RPTOR NM_020761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.367
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.348 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPTOR	NM_020761.3	MANE Select	c.1509+2507C>T		intron	N/A	NP_065812.1	Q8N122-1
	RPTOR	NM_001163034.2		c.1509+2507C>T		intron	N/A	NP_001156506.1	Q8N122-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPTOR	ENST00000306801.8	TSL:1 MANE Select	c.1509+2507C>T		intron	N/A	ENSP00000307272.3	Q8N122-1
	RPTOR	ENST00000575542.5	TSL:1	n.996+2507C>T		intron	N/A
	RPTOR	ENST00000697423.1		c.1563+2507C>T		intron	N/A	ENSP00000513305.1	A0A8V8TMD9

Frequencies

GnomAD3 genomes AF: 0.171 AC: 26003 AN: 152034 Hom.: 2703 Cov.: 32

Gnomad AFR AF: 0.0689

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.362

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.162

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

GnomAD4 genome AF: 0.171 AC: 26002 AN: 152152 Hom.: 2707 Cov.: 32 AF XY: 0.177 AC XY: 13169 AN XY: 74368

African (AFR) AF: 0.0687 AC: 2853 AN: 41542

American (AMR) AF: 0.262 AC: 4009 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 442 AN: 3468

East Asian (EAS) AF: 0.362 AC: 1853 AN: 5124

South Asian (SAS) AF: 0.292 AC: 1408 AN: 4818

European-Finnish (FIN) AF: 0.219 AC: 2316 AN: 10596

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.186 AC: 12654 AN: 67984

Other (OTH) AF: 0.166 AC: 351 AN: 2112

Alfa AF: 0.179 Hom.: 5872

Bravo AF: 0.170

Asia WGS AF: 0.330 AC: 1144 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.3
DANN	Benign	0.95
PhyloP100		-0.37
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: rs2672890; hg19: chr17-78834207; COSMIC: COSV60805520; COSMIC: COSV60805520;