rs12946049

Variant names:

• chr17-80620869-T-C
• rs12946049
• NM_020761.3:c.163-4822T>C

Variant summary

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

The NM_020761.3(RPTOR):​c.163-4822T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 152,266 control chromosomes in the GnomAD database, including 3,008 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 (3008 hom., cov: 33)
• Consequence: RPTOR NM_020761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.124
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPTOR	NM_020761.3	c.163-4822T>C		intron_variant	Intron 1 of 33	ENST00000306801.8	NP_065812.1
RPTOR	NM_001163034.2	c.163-4822T>C		intron_variant	Intron 1 of 29		NP_001156506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPTOR	ENST00000306801.8	c.163-4822T>C		intron_variant	Intron 1 of 33	1	NM_020761.3	ENSP00000307272.3

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28152 AN: 152146 Hom.: 3010 Cov.: 33

Gnomad AFR AF: 0.0702

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.204

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.203

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

GnomAD4 genome AF: 0.185 AC: 28144 AN: 152266 Hom.: 3008 Cov.: 33 AF XY: 0.184 AC XY: 13718 AN XY: 74462

African (AFR) AF: 0.0701 AC: 2914 AN: 41560

American (AMR) AF: 0.189 AC: 2896 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 705 AN: 3470

East Asian (EAS) AF: 0.280 AC: 1454 AN: 5190

South Asian (SAS) AF: 0.198 AC: 957 AN: 4828

European-Finnish (FIN) AF: 0.205 AC: 2176 AN: 10596

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.241 AC: 16374 AN: 68004

Other (OTH) AF: 0.200 AC: 422 AN: 2108

Alfa AF: 0.206 Hom.: 1083

Bravo AF: 0.177

Asia WGS AF: 0.182 AC: 635 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.3
DANN	Benign	0.28
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: rs12946049; hg19: chr17-78594669;