dbSNP rs1062935: RPTOR:n.5222T>C (chr17-80966057-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000575542.5(RPTOR):n.5222T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 230,630 control chromosomes in the GnomAD database, including 22,913 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 0.40 ( 13589 hom., cov: 27)

Exomes 𝑓: 0.48 ( 9324 hom. )

Consequence

RPTOR
ENST00000575542.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0770

Publications

33 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:

ENSG00000261924 (HGNC:):

ENSG00000261924 links:

Genome browser will be placed here

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=-0.8).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
RPTOR	NM_020761.3 link	c.*1727T>C	3_prime_UTR_variant	Exon 34 of 34	ENST00000306801.8	NP_065812.1	Q8N122-1Q6DKI0
RPTOR	NM_001163034.2 link	c.*1727T>C	3_prime_UTR_variant	Exon 30 of 30		NP_001156506.1	Q8N122-3
LOC400627	NR_148968.1 link	n.*182A>G	downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPTOR	ENST00000306801.8 link	c.*1727T>C		3_prime_UTR_variant	Exon 34 of 34	1	NM_020761.3	ENSP00000307272.3		Q8N122-1

Frequencies

GnomAD3 genomes

AF:

0.401

AC:

60223

AN:

150248

Hom.:

13584

Cov.:

show subpopulations

Gnomad AFR

AF:

0.191

Gnomad AMI

AF:

0.642

Gnomad AMR

AF:

0.522

Gnomad ASJ

AF:

0.514

Gnomad EAS

AF:

0.464

Gnomad SAS

AF:

0.413

Gnomad FIN

AF:

0.428

Gnomad MID

AF:

0.352

Gnomad NFE

AF:

0.481

Gnomad OTH

AF:

0.427

GnomAD4 exome

AF:

0.477

AC:

38267

AN:

80264

Hom.:

9324

Cov.:

AF XY:

0.475

AC XY:

17529

AN XY:

36906

show subpopulations

African (AFR)

AF:

0.199

AC:

771

AN:

3868

American (AMR)

AF:

0.548

AC:

1351

AN:

2466

Ashkenazi Jewish (ASJ)

AF:

0.518

AC:

2628

AN:

5076

East Asian (EAS)

AF:

0.537

AC:

6091

AN:

11340

South Asian (SAS)

AF:

0.393

AC:

274

AN:

698

European-Finnish (FIN)

AF:

0.576

AC:

AN:

Middle Eastern (MID)

AF:

0.496

AC:

241

AN:

486

European-Non Finnish (NFE)

AF:

0.482

AC:

23913

AN:

49576

Other (OTH)

AF:

0.443

AC:

2960

AN:

6688

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

870

1739

2609

3478

4348

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

224

336

448

560

<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:

0.401

AC:

60242

AN:

150366

Hom.:

13589

Cov.:

AF XY:

0.400

AC XY:

29286

AN XY:

73238

show subpopulations

African (AFR)

AF:

0.191

AC:

7857

AN:

41078

American (AMR)

AF:

0.522

AC:

7891

AN:

15116

Ashkenazi Jewish (ASJ)

AF:

0.514

AC:

1777

AN:

3454

East Asian (EAS)

AF:

0.464

AC:

2281

AN:

4914

South Asian (SAS)

AF:

0.412

AC:

1964

AN:

4764

European-Finnish (FIN)

AF:

0.428

AC:

4349

AN:

10156

Middle Eastern (MID)

AF:

0.344

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.482

AC:

32558

AN:

67616

Other (OTH)

AF:

0.427

AC:

886

AN:

2076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

1468

2936

4405

5873

7341

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

568

1136

1704

2272

2840

<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:

0.460

Hom.:

58506

Bravo

AF:

0.404

Asia WGS

AF:

0.407

AC:

1417

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

(source)

DANN

Benign

0.84

PhyloP100

0.077

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