chr17-80545369-G-A

Variant names:

• chr17-80545369-G-A
• rs12602885
• NM_020761.3:c.-261G>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.-261G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 352,010 control chromosomes in the GnomAD database, including 6,889 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 0.16 (2352 hom., cov: 32)
  • Exomes 𝑓: 0.20 (4537 hom.)
• Consequence: RPTOR NM_020761.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.780
• Publications: 18 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]

ENSG00000289764 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.263 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.-261G>A		5_prime_UTR	Exon 1 of 34	NP_065812.1	Q8N122-1
	RPTOR	NM_001163034.2		c.-261G>A		5_prime_UTR	Exon 1 of 30	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.-261G>A		5_prime_UTR	Exon 1 of 34	ENSP00000307272.3	Q8N122-1
	RPTOR	ENST00000570891.5	TSL:1	c.-261G>A		5_prime_UTR	Exon 1 of 9	ENSP00000460136.1	Q8N122-2
	RPTOR	ENST00000697423.1		c.-207G>A		5_prime_UTR	Exon 1 of 34	ENSP00000513305.1	A0A8V8TMD9

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25053 AN: 152068 Hom.: 2351 Cov.: 32

Gnomad AFR AF: 0.0630

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.179

GnomAD4 exome AF: 0.204 AC: 40675 AN: 199824 Hom.: 4537 Cov.: 0 AF XY: 0.203 AC XY: 20608 AN XY: 101618

African (AFR) AF: 0.0662 AC: 422 AN: 6376

American (AMR) AF: 0.155 AC: 1042 AN: 6704

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 1424 AN: 7868

East Asian (EAS) AF: 0.320 AC: 5655 AN: 17684

South Asian (SAS) AF: 0.178 AC: 1572 AN: 8844

European-Finnish (FIN) AF: 0.195 AC: 2401 AN: 12306

Middle Eastern (MID) AF: 0.175 AC: 178 AN: 1020

European-Non Finnish (NFE) AF: 0.204 AC: 25576 AN: 125576

Other (OTH) AF: 0.179 AC: 2405 AN: 13446

GnomAD4 genome AF: 0.165 AC: 25062 AN: 152186 Hom.: 2352 Cov.: 32 AF XY: 0.165 AC XY: 12285 AN XY: 74388

African (AFR) AF: 0.0634 AC: 2634 AN: 41564

American (AMR) AF: 0.174 AC: 2656 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 642 AN: 3472

East Asian (EAS) AF: 0.275 AC: 1423 AN: 5170

South Asian (SAS) AF: 0.191 AC: 919 AN: 4822

European-Finnish (FIN) AF: 0.181 AC: 1914 AN: 10582

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.210 AC: 14259 AN: 67962

Other (OTH) AF: 0.176 AC: 372 AN: 2112

Alfa AF: 0.192 Hom.: 8136

Bravo AF: 0.159

Asia WGS AF: 0.176 AC: 615 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	11
DANN	Benign	0.86
PhyloP100		0.78
PromoterAI		-0.038	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=300/0	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: rs12602885; hg19: chr17-78519169; COSMIC: COSV60817980; COSMIC: COSV60817980;