17-80677700-T-C

Variant names:

• chr17-80677700-T-C
• rs4889875
• NM_020761.3:c.349-30141T>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.349-30141T>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
• Publications: 7 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 = 0.84 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020761.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPTOR	NM_020761.3	MANE Select	c.349-30141T>C		intron	N/A	NP_065812.1
	RPTOR	NM_001163034.2		c.349-30141T>C		intron	N/A	NP_001156506.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPTOR	ENST00000306801.8	TSL:1 MANE Select	c.349-30141T>C		intron	N/A	ENSP00000307272.3
	RPTOR	ENST00000570891.5	TSL:1	c.349-30141T>C		intron	N/A	ENSP00000460136.1
	RPTOR	ENST00000697423.1		c.403-30141T>C		intron	N/A	ENSP00000513305.1

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

African (AFR) AF: 0.848 AC: 35179 AN: 41494

American (AMR) AF: 0.525 AC: 8013 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.682 AC: 2366 AN: 3468

East Asian (EAS) AF: 0.605 AC: 3137 AN: 5184

South Asian (SAS) AF: 0.533 AC: 2569 AN: 4818

European-Finnish (FIN) AF: 0.591 AC: 6223 AN: 10530

Middle Eastern (MID) AF: 0.620 AC: 181 AN: 292

European-Non Finnish (NFE) AF: 0.646 AC: 43926 AN: 68002

Other (OTH) AF: 0.674 AC: 1422 AN: 2110

Alfa AF: 0.646 Hom.: 53558

Bravo AF: 0.682

Asia WGS AF: 0.538 AC: 1876 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	4.1
DANN	Benign	0.31
PhyloP100		-0.22
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: rs4889875; hg19: chr17-78651500;