chr17-80584457-C-G

Variant names:

• chr17-80584457-C-G
• rs11655474
• NM_020761.3:c.162+38666C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_020761.3(RPTOR):​c.162+38666C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00224 in 140,350 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. 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 0.0022 (0 hom., cov: 28)
• Consequence: RPTOR NM_020761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.396
• Publications: 5 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

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+38666C>G		intron	N/A	NP_065812.1
	RPTOR	NM_001163034.2		c.162+38666C>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+38666C>G		intron	N/A	ENSP00000307272.3
	RPTOR	ENST00000570891.5	TSL:1	c.162+38666C>G		intron	N/A	ENSP00000460136.1
	RPTOR	ENST00000697423.1		c.216+38666C>G		intron	N/A	ENSP00000513305.1

Frequencies

GnomAD3 genomes AF: 0.00225 AC: 315 AN: 140236 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.00282

Gnomad AMI AF: 0.00113

Gnomad AMR AF: 0.00210

Gnomad ASJ AF: 0.00308

Gnomad EAS AF: 0.00441

Gnomad SAS AF: 0.00325

Gnomad FIN AF: 0.00159

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00173

Gnomad OTH AF: 0.00422

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

GnomAD4 genome AF: 0.00224 AC: 315 AN: 140350 Hom.: 0 Cov.: 28 AF XY: 0.00226 AC XY: 155 AN XY: 68666

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00281 AC: 107 AN: 38036

American (AMR) AF: 0.00210 AC: 29 AN: 13822

Ashkenazi Jewish (ASJ) AF: 0.00308 AC: 10 AN: 3248

East Asian (EAS) AF: 0.00442 AC: 21 AN: 4746

South Asian (SAS) AF: 0.00325 AC: 14 AN: 4304

European-Finnish (FIN) AF: 0.00159 AC: 16 AN: 10034

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 278

European-Non Finnish (NFE) AF: 0.00173 AC: 109 AN: 63082

Other (OTH) AF: 0.00417 AC: 8 AN: 1918

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.5
DANN	Benign	0.63
PhyloP100		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11655474; hg19: chr17-78558257;