dbSNP rs7219896: RPTOR:c.890+10262T>C (chr17-80801771-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 NM_020761.3(RPTOR):c.890+10262T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 151,938 control chromosomes in the GnomAD database, including 4,154 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 0.22 ( 4154 hom., cov: 32)

Exomes 𝑓: 0.19 ( 0 hom. )

Consequence

RPTOR
NM_020761.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.27

Publications

11 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:

ENSG00000262833 (HGNC:):

ENSG00000262833 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=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.317 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
RPTOR	NM_020761.3	MANE Select	c.890+10262T>C	intron	N/A	NP_065812.1
RPTOR	NM_001163034.2		c.890+10262T>C	intron	N/A	NP_001156506.1
LOC101928855	NR_110852.1		n.3073A>G	non_coding_transcript_exon	Exon 4 of 4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
RPTOR	ENST00000306801.8	TSL:1 MANE Select	c.890+10262T>C	intron	N/A	ENSP00000307272.3
RPTOR	ENST00000570891.5	TSL:1	c.890+10262T>C	intron	N/A	ENSP00000460136.1
RPTOR	ENST00000575542.5	TSL:1	n.377+10262T>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.222

AC:

33708

AN:

151804

Hom.:

4139

Cov.:

show subpopulations

Gnomad AFR

AF:

0.321

Gnomad AMI

AF:

0.0724

Gnomad AMR

AF:

0.176

Gnomad ASJ

AF:

0.227

Gnomad EAS

AF:

0.0606

Gnomad SAS

AF:

0.216

Gnomad FIN

AF:

0.234

Gnomad MID

AF:

0.231

Gnomad NFE

AF:

0.185

Gnomad OTH

AF:

0.211

GnomAD4 exome

AF:

0.188

AC:

AN:

Hom.:

Cov.:

AF XY:

0.250

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.333

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.167

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.222

AC:

33766

AN:

151922

Hom.:

4154

Cov.:

AF XY:

0.223

AC XY:

16548

AN XY:

74250

show subpopulations

African (AFR)

AF:

0.322

AC:

13326

AN:

41416

American (AMR)

AF:

0.176

AC:

2686

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.227

AC:

788

AN:

3472

East Asian (EAS)

AF:

0.0609

AC:

314

AN:

5156

South Asian (SAS)

AF:

0.217

AC:

1045

AN:

4824

European-Finnish (FIN)

AF:

0.234

AC:

2464

AN:

10528

Middle Eastern (MID)

AF:

0.228

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.185

AC:

12564

AN:

67924

Other (OTH)

AF:

0.212

AC:

446

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1337

2673

4010

5346

6683

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

348

696

1044

1392

1740

<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:

0.196

Hom.:

11296

Bravo

AF:

0.221

Asia WGS

AF:

0.154

AC:

535

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.038

(source)

DANN

Benign

0.37

PhyloP100

-1.3

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over