chr17-80680544-G-A

Variant names:

• chr17-80680544-G-A
• rs2019154
• NM_020761.3:c.349-27297G>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.349-27297G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 152,066 control chromosomes in the GnomAD database, including 2,849 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 0.18 (2849 hom., cov: 32)
• Consequence: RPTOR NM_020761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.318
• Publications: 3 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 (EAS) allele frequency at 95% confidence interval = 0.234 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.349-27297G>A		intron	N/A	NP_065812.1
	RPTOR	NM_001163034.2		c.349-27297G>A		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.349-27297G>A		intron	N/A	ENSP00000307272.3
	RPTOR	ENST00000570891.5	TSL:1	c.349-27297G>A		intron	N/A	ENSP00000460136.1
	RPTOR	ENST00000697423.1		c.403-27297G>A		intron	N/A	ENSP00000513305.1

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27224 AN: 151948 Hom.: 2852 Cov.: 32

Gnomad AFR AF: 0.0620

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.179 AC: 27214 AN: 152066 Hom.: 2849 Cov.: 32 AF XY: 0.178 AC XY: 13228 AN XY: 74340

African (AFR) AF: 0.0619 AC: 2568 AN: 41488

American (AMR) AF: 0.185 AC: 2821 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 695 AN: 3468

East Asian (EAS) AF: 0.242 AC: 1247 AN: 5150

South Asian (SAS) AF: 0.207 AC: 997 AN: 4822

European-Finnish (FIN) AF: 0.197 AC: 2087 AN: 10578

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

European-Non Finnish (NFE) AF: 0.237 AC: 16139 AN: 67970

Other (OTH) AF: 0.197 AC: 417 AN: 2112

Alfa AF: 0.200 Hom.: 444

Bravo AF: 0.171

Asia WGS AF: 0.165 AC: 576 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	1.8
DANN	Benign	0.54
PhyloP100		-0.32
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: rs2019154; hg19: chr17-78654344;