Genetic Variant FOXO1:c.*106T>C (chr13-40558943-A-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_002015.4(FOXO1):c.*106T>C variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.204 in 395,628 control chromosomes in the GnomAD database, including 8,867 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 0.18 ( 2778 hom., cov: 30)

Exomes 𝑓: 0.22 ( 6089 hom. )

Consequence

FOXO1
NM_002015.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.73

Publications

5 publications found

Variant links:

Genes affected

FOXO1 (HGNC:3819): (forkhead box O1) This gene belongs to the forkhead family of transcription factors which are characterized by a distinct forkhead domain. The specific function of this gene has not yet been determined; however, it may play a role in myogenic growth and differentiation. Translocation of this gene with PAX3 has been associated with alveolar rhabdomyosarcoma. [provided by RefSeq, Jul 2008]

FOXO1 links:

ENSG00000288542 (HGNC:):

ENSG00000288542 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=-0.65).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
FOXO1	NM_002015.4 link	c.*106T>C	3_prime_UTR_variant	Exon 3 of 3	ENST00000379561.6	NP_002006.2	Q12778
FOXO1	XM_011535008.3 link	c.*106T>C	3_prime_UTR_variant	Exon 3 of 3		XP_011533310.1
FOXO1	XM_011535010.3 link	c.*106T>C	3_prime_UTR_variant	Exon 3 of 3		XP_011533312.1
FOXO1	XM_047430204.1 link	c.*106T>C	3_prime_UTR_variant	Exon 3 of 3		XP_047286160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXO1	ENST00000379561.6 link	c.*106T>C		3_prime_UTR_variant	Exon 3 of 3	1	NM_002015.4	ENSP00000368880.4		Q12778
ENSG00000288542	ENST00000636651.2 link	n.1459+566T>C		intron_variant	Intron 2 of 3	5

Frequencies

GnomAD3 genomes

AF:

0.183

AC:

27322

AN:

149000

Hom.:

2776

Cov.:

show subpopulations

Gnomad AFR

AF:

0.101

Gnomad AMI

AF:

0.215

Gnomad AMR

AF:

0.157

Gnomad ASJ

AF:

0.171

Gnomad EAS

AF:

0.111

Gnomad SAS

AF:

0.176

Gnomad FIN

AF:

0.204

Gnomad MID

AF:

0.196

Gnomad NFE

AF:

0.242

Gnomad OTH

AF:

0.175

GnomAD4 exome

AF:

0.216

AC:

53360

AN:

246538

Hom.:

6089

Cov.:

AF XY:

0.219

AC XY:

27357

AN XY:

124958

show subpopulations

African (AFR)

AF:

0.0909

AC:

652

AN:

7176

American (AMR)

AF:

0.153

AC:

1134

AN:

7422

Ashkenazi Jewish (ASJ)

AF:

0.178

AC:

1644

AN:

9230

East Asian (EAS)

AF:

0.142

AC:

3246

AN:

22868

South Asian (SAS)

AF:

0.184

AC:

558

AN:

3026

European-Finnish (FIN)

AF:

0.226

AC:

4804

AN:

21226

Middle Eastern (MID)

AF:

0.209

AC:

270

AN:

1292

European-Non Finnish (NFE)

AF:

0.238

AC:

37665

AN:

157932

Other (OTH)

AF:

0.207

AC:

3387

AN:

16366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

2260

4520

6781

9041

11301

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

160

320

480

640

800

<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:

0.183

AC:

27319

AN:

149090

Hom.:

2778

Cov.:

AF XY:

0.179

AC XY:

12992

AN XY:

72690

show subpopulations

African (AFR)

AF:

0.101

AC:

4061

AN:

40380

American (AMR)

AF:

0.156

AC:

2340

AN:

14974

Ashkenazi Jewish (ASJ)

AF:

0.171

AC:

589

AN:

3444

East Asian (EAS)

AF:

0.111

AC:

561

AN:

5046

South Asian (SAS)

AF:

0.178

AC:

835

AN:

4704

European-Finnish (FIN)

AF:

0.204

AC:

2013

AN:

9864

Middle Eastern (MID)

AF:

0.186

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.242

AC:

16312

AN:

67414

Other (OTH)

AF:

0.174

AC:

360

AN:

2070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

1009

2018

3026

4035

5044

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

300

600

900

1200

1500

<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:

0.220

Hom.:

807

Bravo

AF:

0.173

Asia WGS

AF:

0.151

AC:

522

AN:

3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Benign

0.70

PhyloP100

3.7

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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