1-11107853-C-T

Variant names:

• chr1-11107853-C-T
• rs12117270
• NM_004958.4:c.7634+328G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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]

MTOR Gene-Disease associations (from GenCC):

• macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae), Illumina
• overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004958.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTOR	NM_004958.4	MANE Select	c.7634+328G>A		intron	N/A	NP_004949.1	P42345
	MTOR	NM_001386500.1		c.7634+328G>A		intron	N/A	NP_001373429.1	P42345
	MTOR	NM_001386501.1		c.6386+328G>A		intron	N/A	NP_001373430.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTOR	ENST00000361445.9	TSL:1 MANE Select	c.7634+328G>A		intron	N/A	ENSP00000354558.4	P42345
	MTOR	ENST00000934315.1		c.7688+328G>A		intron	N/A	ENSP00000604374.1
	MTOR	ENST00000934312.1		c.7655+328G>A		intron	N/A	ENSP00000604371.1

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

African (AFR) AF: 0.107 AC: 4436 AN: 41548

American (AMR) AF: 0.0619 AC: 947 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0691 AC: 240 AN: 3472

East Asian (EAS) AF: 0.0856 AC: 444 AN: 5188

South Asian (SAS) AF: 0.124 AC: 599 AN: 4830

European-Finnish (FIN) AF: 0.0535 AC: 567 AN: 10600

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0233 AC: 1586 AN: 68010

Other (OTH) AF: 0.0676 AC: 143 AN: 2114

Alfa AF: 0.0468 Hom.: 35

Bravo AF: 0.0610

Asia WGS AF: 0.111 AC: 386 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.3
DANN	Benign	0.39
PhyloP100		-0.32
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12117270; hg19: chr1-11167910;