rs718206

chr1-11234417-T-Achr1-11234417-T-Cchr1-11234417-T-G

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.2209-152A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.718 in 843,986 control chromosomes in the GnomAD database, including 224,584 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.64 (33811 hom., cov: 32)
  • Exomes 𝑓: 0.74 (190773 hom.)
• Consequence: MTOR NM_004958.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.184

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=-0.91).
• BP6: Variant 1-11234417-T-A is Benign according to our data. Variant chr1-11234417-T-A is described in ClinVar as [Benign]. Clinvar id is 1239514.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-11234417-T-A is described in Lovd as [Benign].
• 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.2209-152A>T		intron_variant		ENST00000361445.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTOR	ENST00000361445.9	c.2209-152A>T		intron_variant		1	NM_004958.4	P1

Frequencies

GnomAD3 genomes AF: 0.643 AC: 97793 AN: 152040 Hom.: 33796 Cov.: 32

Gnomad AFR AF: 0.366

Gnomad AMI AF: 0.752

Gnomad AMR AF: 0.779

Gnomad ASJ AF: 0.656

Gnomad EAS AF: 0.912

Gnomad SAS AF: 0.834

Gnomad FIN AF: 0.745

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.728

Gnomad OTH AF: 0.690

GnomAD4 exome AF: 0.735 AC: 508512 AN: 691830 Hom.: 190773 AF XY: 0.739 AC XY: 264365 AN XY: 357846

Gnomad4 AFR exome AF: 0.340

Gnomad4 AMR exome AF: 0.841

Gnomad4 ASJ exome AF: 0.657

Gnomad4 EAS exome AF: 0.898

Gnomad4 SAS exome AF: 0.827

Gnomad4 FIN exome AF: 0.745

Gnomad4 NFE exome AF: 0.724

Gnomad4 OTH exome AF: 0.725

GnomAD4 genome AF: 0.643 AC: 97845 AN: 152156 Hom.: 33811 Cov.: 32 AF XY: 0.650 AC XY: 48371 AN XY: 74404

Gnomad4 AFR AF: 0.366

Gnomad4 AMR AF: 0.779

Gnomad4 ASJ AF: 0.656

Gnomad4 EAS AF: 0.912

Gnomad4 SAS AF: 0.834

Gnomad4 FIN AF: 0.745

Gnomad4 NFE AF: 0.728

Gnomad4 OTH AF: 0.693

Alfa AF: 0.670 Hom.: 4439

Bravo AF: 0.633

Asia WGS AF: 0.852 AC: 2965 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	-0.91
Cadd	Benign	0.84
Dann	Benign	0.64

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: rs718206; hg19: chr1-11294474;