rs7219896

chr17-80801771-T-C

Variant summary

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

The NM_020761.3(RPTOR):c.890+10262T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 151,938 control chromosomes in the GnomAD database, including 4,154 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 0.22 (4154 hom., cov: 32)
  • Exomes 𝑓: 0.19 (0 hom.)
• Consequence: RPTOR NM_020761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPTOR	NM_020761.3	c.890+10262T>C		intron_variant		ENST00000306801.8
LOC101928855	NR_110852.1	n.3073A>G		non_coding_transcript_exon_variant	4/4
RPTOR	NM_001163034.2	c.890+10262T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPTOR	ENST00000306801.8	c.890+10262T>C		intron_variant		1	NM_020761.3	P1
	ENST00000570335.1	n.3073A>G		non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33708 AN: 151804 Hom.: 4139 Cov.: 32

Gnomad AFR AF: 0.321

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.0606

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.211

GnomAD4 exome AF: 0.188 AC: 3 AN: 16 Hom.: 0 Cov.: 0 AF XY: 0.250 AC XY: 2 AN XY: 8

Gnomad4 FIN exome AF: 0.333

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.222 AC: 33766 AN: 151922 Hom.: 4154 Cov.: 32 AF XY: 0.223 AC XY: 16548 AN XY: 74250

Gnomad4 AFR AF: 0.322

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.227

Gnomad4 EAS AF: 0.0609

Gnomad4 SAS AF: 0.217

Gnomad4 FIN AF: 0.234

Gnomad4 NFE AF: 0.185

Gnomad4 OTH AF: 0.212

Alfa AF: 0.195 Hom.: 4440

Bravo AF: 0.221

Asia WGS AF: 0.154 AC: 535 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.038
Dann	Benign	0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs7219896; hg19: chr17-78775571;