1-11107853-C-T

Position:

• chr1-11107853-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.7634+328G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0591 in 152,264 control chromosomes in the GnomAD database, including 375 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.059 (375 hom., cov: 32)
• Consequence: MTOR NM_004958.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.315

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=-0.89).
• BP6: Variant 1-11107853-C-T is Benign according to our data. Variant chr1-11107853-C-T is described in ClinVar as [Benign]. Clinvar id is 1283465.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTOR	NM_004958.4	c.7634+328G>A		intron_variant		ENST00000361445.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTOR	ENST00000361445.9	c.7634+328G>A		intron_variant		1	NM_004958.4	P1

Frequencies

GnomAD3 genomes AF: 0.0590 AC: 8980 AN: 152144 Hom.: 370 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.0242

Gnomad AMR AF: 0.0616

Gnomad ASJ AF: 0.0691

Gnomad EAS AF: 0.0856

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.0535

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0233

Gnomad OTH AF: 0.0669

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

GnomAD4 genome AF: 0.0591 AC: 9000 AN: 152264 Hom.: 375 Cov.: 32 AF XY: 0.0616 AC XY: 4583 AN XY: 74446

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.0619

Gnomad4 ASJ AF: 0.0691

Gnomad4 EAS AF: 0.0856

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.0535

Gnomad4 NFE AF: 0.0233

Gnomad4 OTH AF: 0.0676

Alfa AF: 0.0445 Hom.: 28

Bravo AF: 0.0610

Asia WGS AF: 0.111 AC: 386 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 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.3
DANN	Benign	0.39

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: rs12117270; hg19: chr1-11167910;