rs4969444

chr17-80806210-G-Achr17-80806210-G-C

Variant summary

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

The NM_020761.3(RPTOR):c.890+14701G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 151,926 control chromosomes in the GnomAD database, including 3,425 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 0.21 (3425 hom., cov: 33)
• Consequence: RPTOR NM_020761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.571

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPTOR	NM_020761.3	c.890+14701G>A		intron_variant		ENST00000306801.8
RPTOR	NM_001163034.2	c.890+14701G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPTOR	ENST00000306801.8	c.890+14701G>A		intron_variant		1	NM_020761.3	P1

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31195 AN: 151808 Hom.: 3411 Cov.: 33

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.0725

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.0605

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.204

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

GnomAD4 genome AF: 0.206 AC: 31248 AN: 151926 Hom.: 3425 Cov.: 33 AF XY: 0.207 AC XY: 15353 AN XY: 74252

Gnomad4 AFR AF: 0.263

Gnomad4 AMR AF: 0.171

Gnomad4 ASJ AF: 0.226

Gnomad4 EAS AF: 0.0608

Gnomad4 SAS AF: 0.215

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.185

Gnomad4 OTH AF: 0.204

Alfa AF: 0.173 Hom.: 1288

Bravo AF: 0.201

Asia WGS AF: 0.150 AC: 522 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	9.1
Dann	Benign	0.49

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: rs4969444; hg19: chr17-78780010;