chr17-80608893-G-A

Variant names:

• chr17-80608893-G-A
• rs8080957
• NM_020761.3:c.163-16798G>A

Variant summary

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

The NM_020761.3(RPTOR):​c.163-16798G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 152,074 control chromosomes in the GnomAD database, including 10,654 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 0.37 (10654 hom., cov: 32)
• Consequence: RPTOR NM_020761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.617
• Publications: 11 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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.387 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPTOR	NM_020761.3	MANE Select	c.163-16798G>A		intron	N/A	NP_065812.1	Q8N122-1
	RPTOR	NM_001163034.2		c.163-16798G>A		intron	N/A	NP_001156506.1	Q8N122-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPTOR	ENST00000306801.8	TSL:1 MANE Select	c.163-16798G>A		intron	N/A	ENSP00000307272.3	Q8N122-1
	RPTOR	ENST00000570891.5	TSL:1	c.163-16798G>A		intron	N/A	ENSP00000460136.1	Q8N122-2
	RPTOR	ENST00000697423.1		c.217-16798G>A		intron	N/A	ENSP00000513305.1	A0A8V8TMD9

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56500 AN: 151956 Hom.: 10641 Cov.: 32

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.397

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.391

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

GnomAD4 genome AF: 0.372 AC: 56514 AN: 152074 Hom.: 10654 Cov.: 32 AF XY: 0.371 AC XY: 27545 AN XY: 74334

African (AFR) AF: 0.365 AC: 15131 AN: 41482

American (AMR) AF: 0.290 AC: 4429 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.468 AC: 1625 AN: 3472

East Asian (EAS) AF: 0.303 AC: 1569 AN: 5176

South Asian (SAS) AF: 0.344 AC: 1658 AN: 4820

European-Finnish (FIN) AF: 0.397 AC: 4194 AN: 10560

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.391 AC: 26600 AN: 67958

Other (OTH) AF: 0.392 AC: 827 AN: 2110

Alfa AF: 0.383 Hom.: 44884

Bravo AF: 0.366

Asia WGS AF: 0.338 AC: 1174 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.3
DANN	Benign	0.64
PhyloP100		-0.62
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: rs8080957; hg19: chr17-78582693;