dbSNP rs2802292: FOXO3:c.621+25486G>T (chr6-108587315-G-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001455.4(FOXO3):c.621+25486G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.503 in 151,818 control chromosomes in the GnomAD database, including 21,333 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.50 ( 21333 hom., cov: 30)

Consequence

FOXO3
NM_001455.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.02

Publications

123 publications found

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:

ENSG00000294744 (HGNC:):

ENSG00000294744 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 6-108587315-G-T is Benign according to our data. Variant chr6-108587315-G-T is described in ClinVar as Benign. ClinVar VariationId is 1269978.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXO3	NM_001455.4 link	c.621+25486G>T		intron_variant	Intron 1 of 2	ENST00000406360.2	NP_001446.1	O43524-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
FOXO3	ENST00000406360.2 link	c.621+25486G>T	intron_variant	Intron 1 of 2	1	NM_001455.4	ENSP00000385824.1	O43524-1
FOXO3	ENST00000343882.10 link	c.621+25486G>T	intron_variant	Intron 2 of 3	1		ENSP00000339527.6	O43524-1
ENSG00000294744	ENST00000725671.1 link	n.452+19766G>T	intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.503

AC:

76266

AN:

151700

Hom.:

21326

Cov.:

show subpopulations

Gnomad AFR

AF:

0.243

Gnomad AMI

AF:

0.742

Gnomad AMR

AF:

0.586

Gnomad ASJ

AF:

0.628

Gnomad EAS

AF:

0.683

Gnomad SAS

AF:

0.455

Gnomad FIN

AF:

0.566

Gnomad MID

AF:

0.437

Gnomad NFE

AF:

0.612

Gnomad OTH

AF:

0.506

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

GnomAD4 genome

AF:

0.503

AC:

76313

AN:

151818

Hom.:

21333

Cov.:

AF XY:

0.504

AC XY:

37371

AN XY:

74154

show subpopulations

African (AFR)

AF:

0.243

AC:

10072

AN:

41386

American (AMR)

AF:

0.586

AC:

8936

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.628

AC:

2179

AN:

3470

East Asian (EAS)

AF:

0.683

AC:

3515

AN:

5146

South Asian (SAS)

AF:

0.456

AC:

2201

AN:

4822

European-Finnish (FIN)

AF:

0.566

AC:

5964

AN:

10534

Middle Eastern (MID)

AF:

0.442

AC:

130

AN:

294

European-Non Finnish (NFE)

AF:

0.612

AC:

41573

AN:

67910

Other (OTH)

AF:

0.508

AC:

1066

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1681

3362

5042

6723

8404

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

666

1332

1998

2664

3330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.561

Hom.:

9545

Bravo

AF:

0.497

Asia WGS

AF:

0.528

AC:

1838

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 18, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 29733381) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.20

(source)

DANN

Benign

0.48

PhyloP100

-1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over