Genetic Variant FOXO1:c.630+45688C>A (chr13-40619895-G-T) – 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.630+45688C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0671 in 709,276 control chromosomes in the GnomAD database, including 4,042 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 0.053 ( 592 hom., cov: 32)

Exomes 𝑓: 0.071 ( 3450 hom. )

Consequence

FOXO1
NM_002015.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.27

Publications

8 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:

RLIMP1 (HGNC:39682): (ring finger protein, LIM domain interacting pseudogene 1)

RLIMP1 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 (EAS) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002015.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXO1	NM_002015.4	MANE Select	c.630+45688C>A		intron	N/A	NP_002006.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
FOXO1	ENST00000379561.6	TSL:1 MANE Select	c.630+45688C>A	intron	N/A	ENSP00000368880.4
RLIMP1	ENST00000339626.5	TSL:6	n.833G>T	non_coding_transcript_exon	Exon 2 of 3
FOXO1	ENST00000655267.1		n.333+45688C>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0530

AC:

8056

AN:

152126

Hom.:

576

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0194

Gnomad AMI

AF:

0.116

Gnomad AMR

AF:

0.0880

Gnomad ASJ

AF:

0.0251

Gnomad EAS

AF:

0.381

Gnomad SAS

AF:

0.113

Gnomad FIN

AF:

0.0874

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0312

Gnomad OTH

AF:

0.0623

GnomAD4 exome

AF:

0.0709

AC:

39517

AN:

557032

Hom.:

3450

Cov.:

AF XY:

0.0712

AC XY:

21608

AN XY:

303466

show subpopulations

African (AFR)

AF:

0.0181

AC:

285

AN:

15708

American (AMR)

AF:

0.110

AC:

3949

AN:

35762

Ashkenazi Jewish (ASJ)

AF:

0.0229

AC:

387

AN:

16936

East Asian (EAS)

AF:

0.369

AC:

12324

AN:

33372

South Asian (SAS)

AF:

0.105

AC:

6324

AN:

60324

European-Finnish (FIN)

AF:

0.0863

AC:

4054

AN:

46972

Middle Eastern (MID)

AF:

0.0449

AC:

168

AN:

3744

European-Non Finnish (NFE)

AF:

0.0321

AC:

10093

AN:

314764

Other (OTH)

AF:

0.0656

AC:

1933

AN:

29450

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

1455

2909

4364

5818

7273

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

288

576

864

1152

1440

<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:

0.0532

AC:

8098

AN:

152244

Hom.:

592

Cov.:

AF XY:

0.0597

AC XY:

4441

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.0195

AC:

810

AN:

41556

American (AMR)

AF:

0.0895

AC:

1369

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0251

AC:

AN:

3468

East Asian (EAS)

AF:

0.381

AC:

1969

AN:

5164

South Asian (SAS)

AF:

0.113

AC:

544

AN:

4822

European-Finnish (FIN)

AF:

0.0874

AC:

926

AN:

10598

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0312

AC:

2125

AN:

68020

Other (OTH)

AF:

0.0701

AC:

148

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

369

737

1106

1474

1843

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

196

294

392

490

<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:

0.0379

Hom.:

256

Bravo

AF:

0.0544

Asia WGS

AF:

0.267

AC:

926

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

9.4

(source)

DANN

Benign

0.58

PhyloP100

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over