chr17-80731492-G-A

Variant names:

• chr17-80731492-G-A
• rs12603074
• NM_020761.3:c.654+786G>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.654+786G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 152,122 control chromosomes in the GnomAD database, including 2,902 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 0.18 (2902 hom., cov: 32)
• Consequence: RPTOR NM_020761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.508
• Publications: 4 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPTOR	NM_020761.3	c.654+786G>A		intron_variant	Intron 5 of 33	ENST00000306801.8	NP_065812.1
RPTOR	NM_001163034.2	c.654+786G>A		intron_variant	Intron 5 of 29		NP_001156506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPTOR	ENST00000306801.8	c.654+786G>A		intron_variant	Intron 5 of 33	1	NM_020761.3	ENSP00000307272.3

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27282 AN: 152004 Hom.: 2905 Cov.: 32

Gnomad AFR AF: 0.0589

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.179 AC: 27275 AN: 152122 Hom.: 2902 Cov.: 32 AF XY: 0.179 AC XY: 13279 AN XY: 74352

African (AFR) AF: 0.0589 AC: 2445 AN: 41536

American (AMR) AF: 0.190 AC: 2910 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 695 AN: 3470

East Asian (EAS) AF: 0.241 AC: 1244 AN: 5172

South Asian (SAS) AF: 0.210 AC: 1012 AN: 4812

European-Finnish (FIN) AF: 0.198 AC: 2087 AN: 10566

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.239 AC: 16223 AN: 67970

Other (OTH) AF: 0.196 AC: 414 AN: 2110

Alfa AF: 0.222 Hom.: 1998

Bravo AF: 0.172

Asia WGS AF: 0.164 AC: 573 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	1.4
DANN	Benign	0.61
PhyloP100		-0.51
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: rs12603074; hg19: chr17-78705292;