Genetic Variant FOXO6:p.Leu437Leu (chr1-41382511-C-T) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP6_ModerateBP7BS2

The ENST00000641094.2(FOXO6):c.1309C>T(p.Leu437Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00251 in 1,253,834 control chromosomes in the GnomAD database, including 16 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0036 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0024 ( 12 hom. )

Consequence

FOXO6
ENST00000641094.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.209

Publications

0 publications found

Variant links:

Genes affected

FOXO6 (HGNC:24814): (forkhead box O6) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in positive regulation of dendritic spine development and regulation of transcription by RNA polymerase II. Predicted to be located in cytoplasm. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

FOXO6 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP6

Variant 1-41382511-C-T is Benign according to our data. Variant chr1-41382511-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3898151.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.209 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXO6	NM_001291281.3 link	c.1309C>T	p.Leu437Leu	synonymous_variant	Exon 3 of 3		NP_001278210.2	A0A1X9RU27

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	Protein	UniProt
FOXO6	ENST00000641094.2 link	c.1309C>T	p.Leu437Leu	synonymous_variant	Exon 3 of 3		ENSP00000493184.1	A8MYZ6
FOXO6	ENST00000686812.1 link	c.925C>T	p.Leu309Leu	synonymous_variant	Exon 3 of 3		ENSP00000509631.1	A0A8I5QKU9
FOXO6	ENST00000372591.1 link	n.1319C>T		non_coding_transcript_exon_variant	Exon 2 of 2	5

Frequencies

GnomAD3 genomes

AF:

0.00356

AC:

539

AN:

151266

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000218

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0368

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00214

Gnomad OTH

AF:

0.00193

GnomAD2 exomes

AF:

0.00533

AC:

555

AN:

104114

AF XY:

0.00472

show subpopulations

Gnomad AFR exome

AF:

0.000700

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0297

Gnomad NFE exome

AF:

0.00233

Gnomad OTH exome

AF:

0.00175

GnomAD4 exome

AF:

0.00237

AC:

2612

AN:

1102460

Hom.:

Cov.:

AF XY:

0.00231

AC XY:

1248

AN XY:

540504

show subpopulations

African (AFR)

AF:

0.0000997

AC:

AN:

20062

American (AMR)

AF:

0.0000467

AC:

AN:

21396

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14264

East Asian (EAS)

AF:

0.00

AC:

AN:

7484

South Asian (SAS)

AF:

0.00

AC:

AN:

69588

European-Finnish (FIN)

AF:

0.0282

AC:

739

AN:

26164

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4258

European-Non Finnish (NFE)

AF:

0.00202

AC:

1818

AN:

900130

Other (OTH)

AF:

0.00133

AC:

AN:

39114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

139

278

418

557

696

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00356

AC:

539

AN:

151374

Hom.:

Cov.:

AF XY:

0.00506

AC XY:

374

AN XY:

73946

show subpopulations

African (AFR)

AF:

0.000218

AC:

AN:

41352

American (AMR)

AF:

0.00

AC:

AN:

15234

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3460

East Asian (EAS)

AF:

0.00

AC:

AN:

5120

South Asian (SAS)

AF:

0.00

AC:

AN:

4804

European-Finnish (FIN)

AF:

0.0368

AC:

381

AN:

10348

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.00214

AC:

145

AN:

67762

Other (OTH)

AF:

0.00191

AC:

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

106

132

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00232

Hom.:

Bravo

AF:

0.000933

Asia WGS

AF:

0.000582

AC:

AN:

3450

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

FOXO6: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.22

CADD

Benign

(source)

DANN

Uncertain

0.99

PhyloP100

0.21

Mutation Taster

=89/11

polymorphism

(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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1-41382511-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over