chr17-80575639-C-T

Variant names:

• chr17-80575639-C-T
• rs4890047
• NM_020761.3:c.162+29848C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020761.3(RPTOR):​c.162+29848C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 152,042 control chromosomes in the GnomAD database, including 6,954 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 0.29 (6954 hom., cov: 32)
• Consequence: RPTOR NM_020761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.561
• Publications: 6 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]

LOC105371922 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.06).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPTOR	NM_020761.3	c.162+29848C>T		intron_variant	Intron 1 of 33	ENST00000306801.8	NP_065812.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPTOR	ENST00000306801.8	c.162+29848C>T		intron_variant	Intron 1 of 33	1	NM_020761.3	ENSP00000307272.3

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44707 AN: 151924 Hom.: 6932 Cov.: 32

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.263

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

GnomAD4 genome AF: 0.294 AC: 44769 AN: 152042 Hom.: 6954 Cov.: 32 AF XY: 0.301 AC XY: 22390 AN XY: 74340

African (AFR) AF: 0.285 AC: 11814 AN: 41462

American (AMR) AF: 0.411 AC: 6274 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 709 AN: 3472

East Asian (EAS) AF: 0.419 AC: 2160 AN: 5160

South Asian (SAS) AF: 0.383 AC: 1845 AN: 4822

European-Finnish (FIN) AF: 0.345 AC: 3650 AN: 10580

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.256 AC: 17387 AN: 67964

Other (OTH) AF: 0.267 AC: 563 AN: 2110

Alfa AF: 0.292 Hom.: 1166

Bravo AF: 0.301

Asia WGS AF: 0.414 AC: 1435 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	2.1
DANN	Benign	0.82
PhyloP100		-0.56
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: rs4890047; hg19: chr17-78549439;