Variant 6-108663580-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001455.4(FOXO3):c.747G>A(p.Arg249=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00669 in 1,613,668 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0056 ( 3 hom., cov: 31)

Exomes 𝑓: 0.0068 ( 38 hom. )

Consequence

FOXO3
NM_001455.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.119

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 6-108663580-G-A is Benign according to our data. Variant chr6-108663580-G-A is described in ClinVar as [Benign]. Clinvar id is 769687.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.119 with no splicing effect.

BS2

High AC in GnomAd4 at 853 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXO3	NM_001455.4 linkuse as main transcript	c.747G>A	p.Arg249=	synonymous_variant	2/3	ENST00000406360.2	NP_001446.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXO3	ENST00000406360.2 linkuse as main transcript	c.747G>A	p.Arg249=	synonymous_variant	2/3	1	NM_001455.4	ENSP00000385824	P1	O43524-1
FOXO3	ENST00000343882.10 linkuse as main transcript	c.747G>A	p.Arg249=	synonymous_variant	3/4	1		ENSP00000339527	P1	O43524-1
FOXO3	ENST00000540898.1 linkuse as main transcript	c.87G>A	p.Arg29=	synonymous_variant	2/3	1		ENSP00000446316		O43524-2

Frequencies

GnomAD3 genomes

AF:

0.00561

AC:

853

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00314

Gnomad ASJ

AF:

0.00951

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.00781

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00901

Gnomad OTH

AF:

0.00716

GnomAD3 exomes

AF:

0.00581

AC:

1437

AN:

247332

Hom.:

AF XY:

0.00588

AC XY:

791

AN XY:

134536

show subpopulations

Gnomad AFR exome

AF:

0.00132

Gnomad AMR exome

AF:

0.00221

Gnomad ASJ exome

AF:

0.0109

Gnomad EAS exome

AF:

0.0000546

Gnomad SAS exome

AF:

0.00180

Gnomad FIN exome

AF:

0.00695

Gnomad NFE exome

AF:

0.00886

Gnomad OTH exome

AF:

0.00666

GnomAD4 exome

AF:

0.00680

AC:

9940

AN:

1461382

Hom.:

Cov.:

AF XY:

0.00672

AC XY:

4888

AN XY:

726992

show subpopulations

Gnomad4 AFR exome

AF:

0.00123

Gnomad4 AMR exome

AF:

0.00242

Gnomad4 ASJ exome

AF:

0.0106

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00203

Gnomad4 FIN exome

AF:

0.00644

Gnomad4 NFE exome

AF:

0.00776

Gnomad4 OTH exome

AF:

0.00558

GnomAD4 genome

AF:

0.00560

AC:

853

AN:

152286

Hom.:

Cov.:

AF XY:

0.00526

AC XY:

392

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00120

Gnomad4 AMR

AF:

0.00314

Gnomad4 ASJ

AF:

0.00951

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00187

Gnomad4 FIN

AF:

0.00781

Gnomad4 NFE

AF:

0.00901

Gnomad4 OTH

AF:

0.00709

Alfa

AF:

0.00841

Hom.:

Bravo

AF:

0.00467

EpiCase

AF:

0.00763

EpiControl

AF:

0.00795

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

May 30, 2018

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

8.2

DANN

Benign

0.59

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