Genetic Variant RPTOR:c.2520+111A>G (chr17-80909040-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020761.3(RPTOR):c.2520+111A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 740,206 control chromosomes in the GnomAD database, including 43,833 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 0.34 ( 9213 hom., cov: 33)

Exomes 𝑓: 0.34 ( 34620 hom. )

Consequence

RPTOR
NM_020761.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0170

Publications

12 publications found

Variant links:

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]

RPTOR links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPTOR	NM_020761.3 link	c.2520+111A>G		intron_variant	Intron 21 of 33	ENST00000306801.8	NP_065812.1
RPTOR	NM_001163034.2 link	c.2046+111A>G		intron_variant	Intron 17 of 29		NP_001156506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPTOR	ENST00000306801.8 link	c.2520+111A>G		intron_variant	Intron 21 of 33	1	NM_020761.3	ENSP00000307272.3

Frequencies

GnomAD3 genomes

AF:

0.343

AC:

52172

AN:

152030

Hom.:

9206

Cov.:

show subpopulations

Gnomad AFR

AF:

0.395

Gnomad AMI

AF:

0.249

Gnomad AMR

AF:

0.322

Gnomad ASJ

AF:

0.301

Gnomad EAS

AF:

0.476

Gnomad SAS

AF:

0.345

Gnomad FIN

AF:

0.249

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.325

Gnomad OTH

AF:

0.325

GnomAD4 exome

AF:

0.339

AC:

199315

AN:

588058

Hom.:

34620

AF XY:

0.339

AC XY:

106641

AN XY:

314746

show subpopulations

African (AFR)

AF:

0.395

AC:

6262

AN:

15854

American (AMR)

AF:

0.313

AC:

10489

AN:

33508

Ashkenazi Jewish (ASJ)

AF:

0.316

AC:

5289

AN:

16738

East Asian (EAS)

AF:

0.488

AC:

17233

AN:

35330

South Asian (SAS)

AF:

0.353

AC:

20810

AN:

58888

European-Finnish (FIN)

AF:

0.270

AC:

11356

AN:

42010

Middle Eastern (MID)

AF:

0.324

AC:

734

AN:

2266

European-Non Finnish (NFE)

AF:

0.331

AC:

116574

AN:

352444

Other (OTH)

AF:

0.341

AC:

10568

AN:

31020

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

6545

13091

19636

26182

32727

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1340

2680

4020

5360

6700

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.343

AC:

52203

AN:

152148

Hom.:

9213

Cov.:

AF XY:

0.339

AC XY:

25237

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.394

AC:

16361

AN:

41488

American (AMR)

AF:

0.322

AC:

4927

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.301

AC:

1045

AN:

3472

East Asian (EAS)

AF:

0.477

AC:

2471

AN:

5180

South Asian (SAS)

AF:

0.344

AC:

1655

AN:

4810

European-Finnish (FIN)

AF:

0.249

AC:

2633

AN:

10590

Middle Eastern (MID)

AF:

0.282

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.325

AC:

22112

AN:

67992

Other (OTH)

AF:

0.326

AC:

689

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1761

3523

5284

7046

8807

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

524

1048

1572

2096

2620

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.324

Hom.:

9554

Bravo

AF:

0.351

Asia WGS

AF:

0.421

AC:

1462

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.17

(source)

DANN

Benign

0.36

PhyloP100

0.017

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over