17-80677700-T-C

Variant names:

• chr17-80677700-T-C
• rs4889875
• NM_020761.3:c.349-30141T>C

Variant summary

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

The NM_020761.3(RPTOR):​c.349-30141T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.681 in 152,082 control chromosomes in the GnomAD database, including 36,262 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 0.68 (36262 hom., cov: 32)
• Consequence: RPTOR NM_020761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.221

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPTOR	NM_020761.3	c.349-30141T>C		intron_variant	Intron 3 of 33	ENST00000306801.8	NP_065812.1
RPTOR	NM_001163034.2	c.349-30141T>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.349-30141T>C		intron_variant	Intron 3 of 33	1	NM_020761.3	ENSP00000307272.3

Frequencies

GnomAD3 genomes AF: 0.681 AC: 103452 AN: 151962 Hom.: 36233 Cov.: 32

Gnomad AFR AF: 0.848

Gnomad AMI AF: 0.560

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.682

Gnomad EAS AF: 0.606

Gnomad SAS AF: 0.532

Gnomad FIN AF: 0.591

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.646

Gnomad OTH AF: 0.677

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

GnomAD4 genome AF: 0.681 AC: 103526 AN: 152082 Hom.: 36262 Cov.: 32 AF XY: 0.672 AC XY: 49920 AN XY: 74322

Gnomad4 AFR AF: 0.848

Gnomad4 AMR AF: 0.525

Gnomad4 ASJ AF: 0.682

Gnomad4 EAS AF: 0.605

Gnomad4 SAS AF: 0.533

Gnomad4 FIN AF: 0.591

Gnomad4 NFE AF: 0.646

Gnomad4 OTH AF: 0.674

Alfa AF: 0.640 Hom.: 41440

Bravo AF: 0.682

Asia WGS AF: 0.538 AC: 1876 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	4.1
DANN	Benign	0.31

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: rs4889875; hg19: chr17-78651500;