rs2024627

Positions:

• chr1-11238733-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004958.4(MTOR):​c.1787-116A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.722 in 796,032 control chromosomes in the GnomAD database, including 213,069 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.65 (33999 hom., cov: 30)
  • Exomes 𝑓: 0.74 (179070 hom.)
• Consequence: MTOR NM_004958.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.887

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 1-11238733-T-C is Benign according to our data. Variant chr1-11238733-T-C is described in ClinVar as [Benign]. Clinvar id is 1225397.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.89 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTOR	NM_004958.4	c.1787-116A>G		intron_variant		ENST00000361445.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTOR	ENST00000361445.9	c.1787-116A>G		intron_variant		1	NM_004958.4	P1

Frequencies

GnomAD3 genomes AF: 0.649 AC: 98256 AN: 151444 Hom.: 33982 Cov.: 30

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.752

Gnomad AMR AF: 0.780

Gnomad ASJ AF: 0.655

Gnomad EAS AF: 0.912

Gnomad SAS AF: 0.833

Gnomad FIN AF: 0.745

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.728

Gnomad OTH AF: 0.696

GnomAD4 exome AF: 0.740 AC: 476630 AN: 644474 Hom.: 179070 AF XY: 0.743 AC XY: 245382 AN XY: 330238

Gnomad4 AFR exome AF: 0.368

Gnomad4 AMR exome AF: 0.835

Gnomad4 ASJ exome AF: 0.657

Gnomad4 EAS exome AF: 0.898

Gnomad4 SAS exome AF: 0.826

Gnomad4 FIN exome AF: 0.749

Gnomad4 NFE exome AF: 0.729

Gnomad4 OTH exome AF: 0.730

GnomAD4 genome AF: 0.649 AC: 98317 AN: 151558 Hom.: 33999 Cov.: 30 AF XY: 0.656 AC XY: 48533 AN XY: 73994

Gnomad4 AFR AF: 0.386

Gnomad4 AMR AF: 0.781

Gnomad4 ASJ AF: 0.655

Gnomad4 EAS AF: 0.912

Gnomad4 SAS AF: 0.833

Gnomad4 FIN AF: 0.745

Gnomad4 NFE AF: 0.728

Gnomad4 OTH AF: 0.699

Alfa AF: 0.664 Hom.: 5118

Bravo AF: 0.639

Asia WGS AF: 0.853 AC: 2969 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.33
DANN	Benign	0.53

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: rs2024627; hg19: chr1-11298790;