17-80920714-G-A

Variant names:

• chr17-80920714-G-A
• rs9897968
• NM_020761.3:c.2521-2010G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020761.3(RPTOR):​c.2521-2010G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 152,262 control chromosomes in the GnomAD database, including 4,621 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 0.24 (4621 hom., cov: 34)
• Consequence: RPTOR NM_020761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.712
• Publications: 12 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.321 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.2521-2010G>A		intron	N/A	NP_065812.1	Q8N122-1
	RPTOR	NM_001163034.2		c.2047-2010G>A		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.2521-2010G>A		intron	N/A	ENSP00000307272.3	Q8N122-1
	RPTOR	ENST00000575542.5	TSL:1	n.2008-2010G>A		intron	N/A
	RPTOR	ENST00000697423.1		c.2575-2010G>A		intron	N/A	ENSP00000513305.1	A0A8V8TMD9

Frequencies

GnomAD3 genomes AF: 0.237 AC: 36052 AN: 152142 Hom.: 4608 Cov.: 34

Gnomad AFR AF: 0.325

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.0922

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.220

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

GnomAD4 genome AF: 0.237 AC: 36097 AN: 152262 Hom.: 4621 Cov.: 34 AF XY: 0.234 AC XY: 17427 AN XY: 74450

African (AFR) AF: 0.326 AC: 13519 AN: 41524

American (AMR) AF: 0.236 AC: 3618 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 512 AN: 3468

East Asian (EAS) AF: 0.0920 AC: 477 AN: 5184

South Asian (SAS) AF: 0.112 AC: 540 AN: 4830

European-Finnish (FIN) AF: 0.246 AC: 2615 AN: 10620

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.208 AC: 14174 AN: 68016

Other (OTH) AF: 0.217 AC: 459 AN: 2114

Alfa AF: 0.208 Hom.: 5985

Bravo AF: 0.243

Asia WGS AF: 0.100 AC: 348 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.89
DANN	Benign	0.81
PhyloP100		-0.71
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: rs9897968; hg19: chr17-78894514; COSMIC: COSV60820899; COSMIC: COSV60820899;