rs17036350

Positions:

• chr1-11111169-C-T

Variant summary

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

The NM_004958.4(MTOR):​c.7367-1440G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0827 in 455,678 control chromosomes in the GnomAD database, including 2,895 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 0.097 (1205 hom., cov: 31)
  • Exomes 𝑓: 0.076 (1690 hom.)
• Consequence: MTOR NM_004958.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.745

Genes affected

MTOR (HGNC:3942): (mechanistic target of rapamycin kinase) The protein encoded by this gene belongs to a family of phosphatidylinositol kinase-related kinases. These kinases mediate cellular responses to stresses such as DNA damage and nutrient deprivation. This kinase is a component of two distinct complexes, mTORC1, which controls protein synthesis, cell growth and proliferation, and mTORC2, which is a regulator of the actin cytoskeleton, and promotes cell survival and cell cycle progression. This protein acts as the target for the cell-cycle arrest and immunosuppressive effects of the FKBP12-rapamycin complex. Inhibitors of mTOR are used in organ transplants as immunosuppressants, and are being evaluated for their therapeutic potential in SARS-CoV-2 infections. Mutations in this gene are associated with Smith-Kingsmore syndrome and somatic focal cortical dysplasia type II. The ANGPTL7 gene is located in an intron of this gene. [provided by RefSeq, Aug 2020]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTOR	NM_004958.4	c.7367-1440G>A		intron_variant		ENST00000361445.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTOR	ENST00000361445.9	c.7367-1440G>A		intron_variant		1	NM_004958.4	P1

Frequencies

GnomAD3 genomes AF: 0.0967 AC: 14692 AN: 151990 Hom.: 1194 Cov.: 31

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.0692

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.0535

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0238

Gnomad OTH AF: 0.0985

GnomAD3 exomes AF: 0.0951 AC: 12157 AN: 127806 Hom.: 897 AF XY: 0.0948 AC XY: 6638 AN XY: 69996

Gnomad AFR exome AF: 0.199

Gnomad AMR exome AF: 0.141

Gnomad ASJ exome AF: 0.0819

Gnomad EAS exome AF: 0.127

Gnomad SAS exome AF: 0.174

Gnomad FIN exome AF: 0.0533

Gnomad NFE exome AF: 0.0226

Gnomad OTH exome AF: 0.0760

GnomAD4 exome AF: 0.0756 AC: 22949 AN: 303570 Hom.: 1690 Cov.: 0 AF XY: 0.0824 AC XY: 14239 AN XY: 172882

Gnomad4 AFR exome AF: 0.194

Gnomad4 AMR exome AF: 0.140

Gnomad4 ASJ exome AF: 0.0798

Gnomad4 EAS exome AF: 0.124

Gnomad4 SAS exome AF: 0.172

Gnomad4 FIN exome AF: 0.0532

Gnomad4 NFE exome AF: 0.0212

Gnomad4 OTH exome AF: 0.0728

GnomAD4 genome AF: 0.0969 AC: 14742 AN: 152108 Hom.: 1205 Cov.: 31 AF XY: 0.102 AC XY: 7556 AN XY: 74370

Gnomad4 AFR AF: 0.202

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.0692

Gnomad4 EAS AF: 0.131

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.0535

Gnomad4 NFE AF: 0.0238

Gnomad4 OTH AF: 0.0989

Alfa AF: 0.0458 Hom.: 249

Bravo AF: 0.104

Asia WGS AF: 0.181 AC: 631 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.37
DANN	Benign	0.26

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: rs17036350; hg19: chr1-11171226; COSMIC: COSV63868668;