Variant rs1130214 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005163.2(AKT1):c.-350G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 208,470 control chromosomes in the GnomAD database, including 9,203 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.30 ( 7346 hom., cov: 33)

Exomes 𝑓: 0.25 ( 1857 hom. )

Consequence

AKT1
NM_005163.2 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.808

Variant links:

Genes affected

AKT1 (HGNC:391): (AKT serine/threonine kinase 1) This gene encodes one of the three members of the human AKT serine-threonine protein kinase family which are often referred to as protein kinase B alpha, beta, and gamma. These highly similar AKT proteins all have an N-terminal pleckstrin homology domain, a serine/threonine-specific kinase domain and a C-terminal regulatory domain. These proteins are phosphorylated by phosphoinositide 3-kinase (PI3K). AKT/PI3K forms a key component of many signalling pathways that involve the binding of membrane-bound ligands such as receptor tyrosine kinases, G-protein coupled receptors, and integrin-linked kinase. These AKT proteins therefore regulate a wide variety of cellular functions including cell proliferation, survival, metabolism, and angiogenesis in both normal and malignant cells. AKT proteins are recruited to the cell membrane by phosphatidylinositol 3,4,5-trisphosphate (PIP3) after phosphorylation of phosphatidylinositol 4,5-bisphosphate (PIP2) by PI3K. Subsequent phosphorylation of both threonine residue 308 and serine residue 473 is required for full activation of the AKT1 protein encoded by this gene. Phosphorylation of additional residues also occurs, for example, in response to insulin growth factor-1 and epidermal growth factor. Protein phosphatases act as negative regulators of AKT proteins by dephosphorylating AKT or PIP3. The PI3K/AKT signalling pathway is crucial for tumor cell survival. Survival factors can suppress apoptosis in a transcription-independent manner by activating AKT1 which then phosphorylates and inactivates components of the apoptotic machinery. AKT proteins also participate in the mammalian target of rapamycin (mTOR) signalling pathway which controls the assembly of the eukaryotic translation initiation factor 4F (eIF4E) complex and this pathway, in addition to responding to extracellular signals from growth factors and cytokines, is disregulated in many cancers. Mutations in this gene are associated with multiple types of cancer and excessive tissue growth including Proteus syndrome and Cowden syndrome 6, and breast, colorectal, and ovarian cancers. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2020]

AKT1 links:

AKT1 (HGNC:):

AKT1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKT1	NM_001382430.1 linkuse as main transcript	c.-257-93G>T		intron_variant		ENST00000649815.2	NP_001369359.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKT1	ENST00000649815.2 linkuse as main transcript	c.-257-93G>T		intron_variant			NM_001382430.1	ENSP00000497822.1		P31749-1

Frequencies

GnomAD3 genomes

AF:

0.302

AC:

45855

AN:

152034

Hom.:

7340

Cov.:

show subpopulations

Gnomad AFR

AF:

0.376

Gnomad AMI

AF:

0.322

Gnomad AMR

AF:

0.247

Gnomad ASJ

AF:

0.252

Gnomad EAS

AF:

0.105

Gnomad SAS

AF:

0.180

Gnomad FIN

AF:

0.294

Gnomad MID

AF:

0.177

Gnomad NFE

AF:

0.297

Gnomad OTH

AF:

0.285

GnomAD4 exome

AF:

0.248

AC:

13982

AN:

56318

Hom.:

1857

Cov.:

AF XY:

0.247

AC XY:

6457

AN XY:

26104

show subpopulations

Gnomad4 AFR exome

AF:

0.369

Gnomad4 AMR exome

AF:

0.228

Gnomad4 ASJ exome

AF:

0.232

Gnomad4 EAS exome

AF:

0.143

Gnomad4 SAS exome

AF:

0.197

Gnomad4 FIN exome

AF:

0.219

Gnomad4 NFE exome

AF:

0.269

Gnomad4 OTH exome

AF:

0.267

GnomAD4 genome

AF:

0.302

AC:

45895

AN:

152152

Hom.:

7346

Cov.:

AF XY:

0.297

AC XY:

22061

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.376

Gnomad4 AMR

AF:

0.247

Gnomad4 ASJ

AF:

0.252

Gnomad4 EAS

AF:

0.105

Gnomad4 SAS

AF:

0.182

Gnomad4 FIN

AF:

0.294

Gnomad4 NFE

AF:

0.297

Gnomad4 OTH

AF:

0.287

Alfa

AF:

0.294

Hom.:

1667

Bravo

AF:

0.303

Asia WGS

AF:

0.137

AC:

475

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.47

DANN

Benign

0.71

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over