Variant chr6-108561712-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_001455.4(FOXO3):c.504C>T(p.Arg168=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00736 in 1,612,114 control chromosomes in the GnomAD database, including 53 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0057 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0075 ( 49 hom. )

Consequence

FOXO3
NM_001455.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.713

Variant links:

Genes affected

FOXO3 (HGNC:3821): (forkhead box O3) This gene belongs to the forkhead family of transcription factors which are characterized by a distinct forkhead domain. This gene likely functions as a trigger for apoptosis through expression of genes necessary for cell death. Translocation of this gene with the MLL gene is associated with secondary acute leukemia. Alternatively spliced transcript variants encoding the same protein have been observed. [provided by RefSeq, Jul 2008]

FOXO3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant 6-108561712-C-T is Benign according to our data. Variant chr6-108561712-C-T is described in ClinVar as [Benign]. Clinvar id is 719100.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.713 with no splicing effect.

BS2

High AC in GnomAd4 at 874 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXO3	NM_001455.4 linkuse as main transcript	c.504C>T	p.Arg168=	synonymous_variant	1/3	ENST00000406360.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXO3	ENST00000406360.2 linkuse as main transcript	c.504C>T	p.Arg168=	synonymous_variant	1/3	1	NM_001455.4	P1	O43524-1
FOXO3	ENST00000343882.10 linkuse as main transcript	c.504C>T	p.Arg168=	synonymous_variant	2/4	1		P1	O43524-1

Frequencies

GnomAD3 genomes

AF:

0.00574

AC:

873

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00123

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00700

Gnomad ASJ

AF:

0.0115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00310

Gnomad FIN

AF:

0.00885

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00809

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.00655

AC:

1618

AN:

246962

Hom.:

AF XY:

0.00655

AC XY:

880

AN XY:

134348

show subpopulations

Gnomad AFR exome

AF:

0.00101

Gnomad AMR exome

AF:

0.00465

Gnomad ASJ exome

AF:

0.0110

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00191

Gnomad FIN exome

AF:

0.00995

Gnomad NFE exome

AF:

0.00923

Gnomad OTH exome

AF:

0.00617

GnomAD4 exome

AF:

0.00753

AC:

10987

AN:

1459782

Hom.:

Cov.:

AF XY:

0.00759

AC XY:

5515

AN XY:

726264

show subpopulations

Gnomad4 AFR exome

AF:

0.00195

Gnomad4 AMR exome

AF:

0.00518

Gnomad4 ASJ exome

AF:

0.0119

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00213

Gnomad4 FIN exome

AF:

0.0111

Gnomad4 NFE exome

AF:

0.00821

Gnomad4 OTH exome

AF:

0.00708

GnomAD4 genome

AF:

0.00574

AC:

874

AN:

152332

Hom.:

Cov.:

AF XY:

0.00532

AC XY:

396

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00125

Gnomad4 AMR

AF:

0.00699

Gnomad4 ASJ

AF:

0.0115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00311

Gnomad4 FIN

AF:

0.00885

Gnomad4 NFE

AF:

0.00809

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.00753

Hom.:

Bravo

AF:

0.00526

EpiCase

AF:

0.00933

EpiControl

AF:

0.00916

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.97

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over