rs7212142

chr17-80650141-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020761.3(RPTOR):c.348+6331G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 152,128 control chromosomes in the GnomAD database, including 20,512 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 0.49 (20512 hom., cov: 33)
• Consequence: RPTOR NM_020761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.633

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.743 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPTOR	NM_020761.3	c.348+6331G>A		intron_variant		ENST00000306801.8
RPTOR	NM_001163034.2	c.348+6331G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPTOR	ENST00000306801.8	c.348+6331G>A		intron_variant		1	NM_020761.3	P1

Frequencies

GnomAD3 genomes AF: 0.492 AC: 74831 AN: 152010 Hom.: 20494 Cov.: 33

Gnomad AFR AF: 0.750

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.537

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.498

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

GnomAD4 genome AF: 0.492 AC: 74895 AN: 152128 Hom.: 20512 Cov.: 33 AF XY: 0.485 AC XY: 36037 AN XY: 74360

Gnomad4 AFR AF: 0.750

Gnomad4 AMR AF: 0.362

Gnomad4 ASJ AF: 0.537

Gnomad4 EAS AF: 0.298

Gnomad4 SAS AF: 0.291

Gnomad4 FIN AF: 0.385

Gnomad4 NFE AF: 0.410

Gnomad4 OTH AF: 0.498

Alfa AF: 0.420 Hom.: 28537

Bravo AF: 0.503

Asia WGS AF: 0.331 AC: 1150 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	4.9
Dann	Benign	0.82

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

Publications

LitVar

Other links and lift over

dbSNP: rs7212142; hg19: chr17-78623941;