chr17-80613425-A-C

Position:

• chr17-80613425-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.163-12266A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 152,250 control chromosomes in the GnomAD database, including 3,059 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 0.16 (3059 hom., cov: 32)
• Consequence: RPTOR NM_020761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.321

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPTOR	NM_020761.3	c.163-12266A>C		intron_variant		ENST00000306801.8	NP_065812.1
RPTOR	NM_001163034.2	c.163-12266A>C		intron_variant			NP_001156506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPTOR	ENST00000306801.8	c.163-12266A>C		intron_variant		1	NM_020761.3	ENSP00000307272	P1

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24992 AN: 152132 Hom.: 3046 Cov.: 32

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.0910

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.0263

Gnomad FIN AF: 0.0545

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.150

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

GnomAD4 genome AF: 0.164 AC: 25040 AN: 152250 Hom.: 3059 Cov.: 32 AF XY: 0.157 AC XY: 11667 AN XY: 74448

Gnomad4 AFR AF: 0.342

Gnomad4 AMR AF: 0.116

Gnomad4 ASJ AF: 0.0910

Gnomad4 EAS AF: 0.00289

Gnomad4 SAS AF: 0.0261

Gnomad4 FIN AF: 0.0545

Gnomad4 NFE AF: 0.112

Gnomad4 OTH AF: 0.149

Alfa AF: 0.117 Hom.: 1554

Bravo AF: 0.175

Asia WGS AF: 0.0400 AC: 142 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.2
DANN	Benign	0.46

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: rs4890055; hg19: chr17-78587225;