1-11233902-C-T

Position:

• chr1-11233902-C-T

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.2331+241G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.649 in 152,038 control chromosomes in the GnomAD database, including 34,122 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.65 (34122 hom., cov: 32)
• Consequence: MTOR NM_004958.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.238

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=-0.93).
• BP6: Variant 1-11233902-C-T is Benign according to our data. Variant chr1-11233902-C-T is described in ClinVar as [Benign]. Clinvar id is 1248357.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	Protein	UniProt
MTOR	NM_004958.4	c.2331+241G>A		intron_variant		ENST00000361445.9	NP_004949.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTOR	ENST00000361445.9	c.2331+241G>A		intron_variant		1	NM_004958.4	ENSP00000354558	P1

Frequencies

GnomAD3 genomes AF: 0.649 AC: 98598 AN: 151920 Hom.: 34105 Cov.: 32

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.753

Gnomad AMR AF: 0.781

Gnomad ASJ AF: 0.655

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: 0.698

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

GnomAD4 genome AF: 0.649 AC: 98659 AN: 152038 Hom.: 34122 Cov.: 32 AF XY: 0.656 AC XY: 48792 AN XY: 74336

Gnomad4 AFR AF: 0.386

Gnomad4 AMR AF: 0.781

Gnomad4 ASJ AF: 0.655

Gnomad4 EAS AF: 0.912

Gnomad4 SAS AF: 0.834

Gnomad4 FIN AF: 0.745

Gnomad4 NFE AF: 0.728

Gnomad4 OTH AF: 0.701

Alfa AF: 0.711 Hom.: 19388

Bravo AF: 0.639

Asia WGS AF: 0.854 AC: 2971 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	-0.93
CADD	Benign	2.0
DANN	Benign	0.71

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: rs11121704; hg19: chr1-11293959;