dbSNP rs9486913: FOXO3:c.622-23818C>G (chr6-108639637-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001455.4(FOXO3):c.622-23818C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 883,824 control chromosomes in the GnomAD database, including 13,881 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 0.19 ( 3277 hom., cov: 32)

Exomes 𝑓: 0.18 ( 10604 hom. )

Consequence

FOXO3
NM_001455.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.65

Publications

11 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXO3	NM_001455.4 link	c.622-23818C>G		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.622-23818C>G	intron_variant	Intron 1 of 2	1	NM_001455.4	ENSP00000385824.1	O43524-1
FOXO3	ENST00000343882.10 link	c.622-23818C>G	intron_variant	Intron 2 of 3	1		ENSP00000339527.6	O43524-1
ENSG00000294744	ENST00000725671.1 link	n.597C>G	non_coding_transcript_exon_variant	Exon 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.195

AC:

29608

AN:

151890

Hom.:

3274

Cov.:

show subpopulations

Gnomad AFR

AF:

0.291

Gnomad AMI

AF:

0.0844

Gnomad AMR

AF:

0.224

Gnomad ASJ

AF:

0.112

Gnomad EAS

AF:

0.0869

Gnomad SAS

AF:

0.167

Gnomad FIN

AF:

0.114

Gnomad MID

AF:

0.301

Gnomad NFE

AF:

0.158

Gnomad OTH

AF:

0.209

GnomAD4 exome

AF:

0.175

AC:

128236

AN:

731816

Hom.:

10604

Cov.:

AF XY:

0.174

AC XY:

59299

AN XY:

339846

show subpopulations

African (AFR)

AF:

0.309

AC:

4440

AN:

14392

American (AMR)

AF:

0.273

AC:

235

AN:

860

Ashkenazi Jewish (ASJ)

AF:

0.113

AC:

503

AN:

4454

East Asian (EAS)

AF:

0.0894

AC:

278

AN:

3108

South Asian (SAS)

AF:

0.192

AC:

2787

AN:

14488

European-Finnish (FIN)

AF:

0.143

AC:

AN:

252

Middle Eastern (MID)

AF:

0.229

AC:

337

AN:

1472

European-Non Finnish (NFE)

AF:

0.172

AC:

115226

AN:

668914

Other (OTH)

AF:

0.184

AC:

4394

AN:

23876

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

4761

9522

14283

19044

23805

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5658

11316

16974

22632

28290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.195

AC:

29624

AN:

152008

Hom.:

3277

Cov.:

AF XY:

0.191

AC XY:

14197

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.290

AC:

12014

AN:

41400

American (AMR)

AF:

0.224

AC:

3422

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.112

AC:

389

AN:

3468

East Asian (EAS)

AF:

0.0869

AC:

449

AN:

5164

South Asian (SAS)

AF:

0.167

AC:

804

AN:

4826

European-Finnish (FIN)

AF:

0.114

AC:

1205

AN:

10598

Middle Eastern (MID)

AF:

0.313

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.158

AC:

10736

AN:

67960

Other (OTH)

AF:

0.207

AC:

436

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1183

2366

3548

4731

5914

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

316

632

948

1264

1580

<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:

0.176

Hom.:

312

Bravo

AF:

0.209

Asia WGS

AF:

0.164

AC:

568

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.22

(source)

DANN

Benign

0.54

PhyloP100

-1.7

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over