dbSNP rs12583418: FOXO1:c.630+44309C>T (chr13-40621274-G-A) – 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+44309C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 755,212 control chromosomes in the GnomAD database, including 43,153 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 0.41 ( 13843 hom., cov: 31)

Exomes 𝑓: 0.28 ( 29310 hom. )

Consequence

FOXO1
NM_002015.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.97

Publications

13 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=-0.6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.712 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXO1	NM_002015.4 link	c.630+44309C>T		intron_variant	Intron 1 of 2	ENST00000379561.6	NP_002006.2	Q12778

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
FOXO1	ENST00000379561.6 link	c.630+44309C>T	intron_variant	Intron 1 of 2	1	NM_002015.4	ENSP00000368880.4	Q12778
RLIMP1	ENST00000339626.5 link	n.1606G>A	non_coding_transcript_exon_variant	Exon 3 of 3	6
FOXO1	ENST00000655267.1 link	n.333+44309C>T	intron_variant	Intron 1 of 2
FOXO1	ENST00000660760.1 link	n.397+11873C>T	intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.408

AC:

62034

AN:

151866

Hom.:

13798

Cov.:

show subpopulations

Gnomad AFR

AF:

0.550

Gnomad AMI

AF:

0.283

Gnomad AMR

AF:

0.410

Gnomad ASJ

AF:

0.295

Gnomad EAS

AF:

0.732

Gnomad SAS

AF:

0.515

Gnomad FIN

AF:

0.358

Gnomad MID

AF:

0.297

Gnomad NFE

AF:

0.306

Gnomad OTH

AF:

0.398

GnomAD4 exome

AF:

0.282

AC:

169978

AN:

603226

Hom.:

29310

Cov.:

AF XY:

0.293

AC XY:

93688

AN XY:

319668

show subpopulations

African (AFR)

AF:

0.473

AC:

5496

AN:

11626

American (AMR)

AF:

0.455

AC:

12398

AN:

27272

Ashkenazi Jewish (ASJ)

AF:

0.241

AC:

3340

AN:

13864

East Asian (EAS)

AF:

0.638

AC:

8333

AN:

13052

South Asian (SAS)

AF:

0.477

AC:

24901

AN:

52156

European-Finnish (FIN)

AF:

0.320

AC:

11314

AN:

35302

Middle Eastern (MID)

AF:

0.284

AC:

998

AN:

3518

European-Non Finnish (NFE)

AF:

0.228

AC:

95852

AN:

420798

Other (OTH)

AF:

0.287

AC:

7346

AN:

25638

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

4103

8207

12310

16414

20517

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2558

5116

7674

10232

12790

<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:

0.409

AC:

62144

AN:

151986

Hom.:

13843

Cov.:

AF XY:

0.414

AC XY:

30790

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.551

AC:

22815

AN:

41444

American (AMR)

AF:

0.411

AC:

6273

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.295

AC:

1020

AN:

3462

East Asian (EAS)

AF:

0.731

AC:

3775

AN:

5162

South Asian (SAS)

AF:

0.515

AC:

2484

AN:

4824

European-Finnish (FIN)

AF:

0.358

AC:

3786

AN:

10562

Middle Eastern (MID)

AF:

0.299

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.306

AC:

20795

AN:

67950

Other (OTH)

AF:

0.403

AC:

850

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1780

3560

5341

7121

8901

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

594

1188

1782

2376

2970

<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:

0.339

Hom.:

4415

Bravo

AF:

0.417

Asia WGS

AF:

0.641

AC:

2225

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

3.4

(source)

DANN

Benign

0.74

PhyloP100

3.0

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over