17-80628572-A-C

Position:

• chr17-80628572-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020761.3(RPTOR):​c.265+2779A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 151,388 control chromosomes in the GnomAD database, including 6,712 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 0.30 (6712 hom., cov: 32)
• Consequence: RPTOR NM_020761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.615

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPTOR	NM_020761.3	c.265+2779A>C		intron_variant		ENST00000306801.8
RPTOR	NM_001163034.2	c.265+2779A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPTOR	ENST00000306801.8	c.265+2779A>C		intron_variant		1	NM_020761.3	P1

Frequencies

GnomAD3 genomes AF: 0.296 AC: 44754 AN: 151278 Hom.: 6709 Cov.: 32

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.323

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

GnomAD4 genome AF: 0.296 AC: 44767 AN: 151388 Hom.: 6712 Cov.: 32 AF XY: 0.296 AC XY: 21932 AN XY: 73992

Gnomad4 AFR AF: 0.295

Gnomad4 AMR AF: 0.234

Gnomad4 ASJ AF: 0.441

Gnomad4 EAS AF: 0.265

Gnomad4 SAS AF: 0.267

Gnomad4 FIN AF: 0.336

Gnomad4 NFE AF: 0.300

Gnomad4 OTH AF: 0.325

Alfa AF: 0.272 Hom.: 2781

Bravo AF: 0.290

Asia WGS AF: 0.278 AC: 965 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.8
DANN	Benign	0.75

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

LitVar

Other links and lift over

dbSNP: rs8071015; hg19: chr17-78602372;