17-80703105-T-C

Variant names:

• chr17-80703105-T-C
• rs4062178
• NM_020761.3:c.349-4736T>C

Variant summary

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

The NM_020761.3(RPTOR):​c.349-4736T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 151,960 control chromosomes in the GnomAD database, including 7,434 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 0.27 (7434 hom., cov: 31)
• Consequence: RPTOR NM_020761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• Publications: 19 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPTOR	NM_020761.3	c.349-4736T>C		intron_variant	Intron 3 of 33	ENST00000306801.8	NP_065812.1
RPTOR	NM_001163034.2	c.349-4736T>C		intron_variant	Intron 3 of 29		NP_001156506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPTOR	ENST00000306801.8	c.349-4736T>C		intron_variant	Intron 3 of 33	1	NM_020761.3	ENSP00000307272.3

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40342 AN: 151840 Hom.: 7412 Cov.: 31

Gnomad AFR AF: 0.528

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.0585

Gnomad SAS AF: 0.0992

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.232

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

GnomAD4 genome AF: 0.266 AC: 40403 AN: 151960 Hom.: 7434 Cov.: 31 AF XY: 0.256 AC XY: 18997 AN XY: 74298

African (AFR) AF: 0.528 AC: 21870 AN: 41382

American (AMR) AF: 0.166 AC: 2542 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 650 AN: 3462

East Asian (EAS) AF: 0.0582 AC: 301 AN: 5168

South Asian (SAS) AF: 0.0997 AC: 480 AN: 4816

European-Finnish (FIN) AF: 0.109 AC: 1157 AN: 10580

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

European-Non Finnish (NFE) AF: 0.186 AC: 12670 AN: 67958

Other (OTH) AF: 0.230 AC: 485 AN: 2110

Alfa AF: 0.203 Hom.: 16092

Bravo AF: 0.282

Asia WGS AF: 0.111 AC: 389 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.20
DANN	Benign	0.21
PhyloP100		-1.2
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: rs4062178; hg19: chr17-78676905;