1-11107703-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.7635-203G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0512 in 152,244 control chromosomes in the GnomAD database, including 272 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.051 (272 hom., cov: 32)
• Consequence: MTOR NM_004958.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.01

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 1-11107703-C-T is Benign according to our data. Variant chr1-11107703-C-T is described in ClinVar as [Benign]. Clinvar id is 1267226.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTOR	NM_004958.4	c.7635-203G>A		intron_variant		ENST00000361445.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTOR	ENST00000361445.9	c.7635-203G>A		intron_variant		1	NM_004958.4	P1

Frequencies

GnomAD3 genomes AF: 0.0511 AC: 7779 AN: 152126 Hom.: 268 Cov.: 32

Gnomad AFR AF: 0.0830

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.0581

Gnomad ASJ AF: 0.0536

Gnomad EAS AF: 0.0852

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.0531

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0225

Gnomad OTH AF: 0.0583

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

GnomAD4 genome AF: 0.0512 AC: 7790 AN: 152244 Hom.: 272 Cov.: 32 AF XY: 0.0539 AC XY: 4015 AN XY: 74438

Gnomad4 AFR AF: 0.0829

Gnomad4 AMR AF: 0.0584

Gnomad4 ASJ AF: 0.0536

Gnomad4 EAS AF: 0.0852

Gnomad4 SAS AF: 0.119

Gnomad4 FIN AF: 0.0531

Gnomad4 NFE AF: 0.0225

Gnomad4 OTH AF: 0.0591

Alfa AF: 0.0121 Hom.: 5

Bravo AF: 0.0526

Asia WGS AF: 0.108 AC: 376 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 27, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.46
Dann	Benign	0.57

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: rs12117235; hg19: chr1-11167760; COSMIC: COSV104421535; COSMIC: COSV104421535;