chr17-80576668-A-G

Variant names:

• chr17-80576668-A-G
• rs4889863
• NM_020761.3:c.162+30877A>G

Variant summary

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

The NM_020761.3(RPTOR):​c.162+30877A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 152,154 control chromosomes in the GnomAD database, including 5,289 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 0.24 (5289 hom., cov: 33)
• Consequence: RPTOR NM_020761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.115
• 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]

LOC105371922 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.404 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.162+30877A>G		intron	N/A	NP_065812.1
	RPTOR	NM_001163034.2		c.162+30877A>G		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.162+30877A>G		intron	N/A	ENSP00000307272.3
	RPTOR	ENST00000570891.5	TSL:1	c.162+30877A>G		intron	N/A	ENSP00000460136.1
	RPTOR	ENST00000697423.1		c.216+30877A>G		intron	N/A	ENSP00000513305.1

Frequencies

GnomAD3 genomes AF: 0.237 AC: 36016 AN: 152036 Hom.: 5272 Cov.: 33

Gnomad AFR AF: 0.0838

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.226

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

GnomAD4 genome AF: 0.237 AC: 36047 AN: 152154 Hom.: 5289 Cov.: 33 AF XY: 0.246 AC XY: 18319 AN XY: 74382

African (AFR) AF: 0.0836 AC: 3473 AN: 41540

American (AMR) AF: 0.391 AC: 5977 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 697 AN: 3470

East Asian (EAS) AF: 0.419 AC: 2166 AN: 5170

South Asian (SAS) AF: 0.383 AC: 1844 AN: 4818

European-Finnish (FIN) AF: 0.345 AC: 3646 AN: 10580

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.256 AC: 17394 AN: 67990

Other (OTH) AF: 0.231 AC: 487 AN: 2112

Alfa AF: 0.254 Hom.: 3243

Bravo AF: 0.236

Asia WGS AF: 0.405 AC: 1404 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.1
DANN	Benign	0.66
PhyloP100		0.12
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: rs4889863; hg19: chr17-78550468;