dbSNP rs4503258: FOXO4:c.*1303C>T (chrX-71103387-C-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_005938.4(FOXO4):c.*1303C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0364 in 162,009 control chromosomes in the GnomAD database, including 313 homozygotes. There are 1,687 hemizygotes in GnomAD. 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 0.038 ( 237 hom., 1315 hem., cov: 21)

Exomes 𝑓: 0.033 ( 76 hom. 372 hem. )

Consequence

FOXO4
NM_005938.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.477

Publications

3 publications found

Variant links:

Genes affected

FOXO4 (HGNC:7139): (forkhead box O4) This gene encodes a member of the O class of winged helix/forkhead transcription factor family. Proteins encoded by this class are regulated by factors involved in growth and differentiation indicating they play a role in these processes. A translocation involving this gene on chromosome X and the homolog of the Drosophila trithorax gene, encoding a DNA binding protein, located on chromosome 11 is associated with leukemia. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2010]

FOXO4 links:

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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=-0.59).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXO4	NM_005938.4 link	c.*1303C>T		3_prime_UTR_variant	Exon 3 of 3	ENST00000374259.8	NP_005929.2	P98177-1
FOXO4	NM_001170931.2 link	c.*1303C>T		3_prime_UTR_variant	Exon 4 of 4		NP_001164402.1	P98177-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXO4	ENST00000374259.8 link	c.*1303C>T		3_prime_UTR_variant	Exon 3 of 3	1	NM_005938.4	ENSP00000363377.3		P98177-1
FOXO4	ENST00000341558.4 link	c.*1303C>T		3_prime_UTR_variant	Exon 4 of 4	5		ENSP00000342209.3		P98177-2

Frequencies

GnomAD3 genomes

AF:

0.0381

AC:

4199

AN:

110200

Hom.:

234

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00664

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.222

Gnomad ASJ

AF:

0.0182

Gnomad EAS

AF:

0.0725

Gnomad SAS

AF:

0.0842

Gnomad FIN

AF:

0.00571

Gnomad MID

AF:

0.00426

Gnomad NFE

AF:

0.0205

Gnomad OTH

AF:

0.0616

GnomAD4 exome

AF:

0.0327

AC:

1695

AN:

51762

Hom.:

Cov.:

AF XY:

0.0305

AC XY:

372

AN XY:

12190

show subpopulations

African (AFR)

AF:

0.00824

AC:

AN:

2427

American (AMR)

AF:

0.248

AC:

404

AN:

1629

Ashkenazi Jewish (ASJ)

AF:

0.0202

AC:

AN:

2968

East Asian (EAS)

AF:

0.0532

AC:

409

AN:

7683

South Asian (SAS)

AF:

0.115

AC:

AN:

399

European-Finnish (FIN)

AF:

0.00289

AC:

AN:

346

Middle Eastern (MID)

AF:

0.00743

AC:

AN:

269

European-Non Finnish (NFE)

AF:

0.0177

AC:

558

AN:

31579

Other (OTH)

AF:

0.0437

AC:

195

AN:

4462

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

120

181

241

301

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0382

AC:

4206

AN:

110247

Hom.:

237

Cov.:

AF XY:

0.0404

AC XY:

1315

AN XY:

32519

show subpopulations

African (AFR)

AF:

0.00662

AC:

201

AN:

30346

American (AMR)

AF:

0.222

AC:

2288

AN:

10292

Ashkenazi Jewish (ASJ)

AF:

0.0182

AC:

AN:

2632

East Asian (EAS)

AF:

0.0725

AC:

249

AN:

3435

South Asian (SAS)

AF:

0.0834

AC:

212

AN:

2543

European-Finnish (FIN)

AF:

0.00571

AC:

AN:

5955

Middle Eastern (MID)

AF:

0.00467

AC:

AN:

214

European-Non Finnish (NFE)

AF:

0.0205

AC:

1077

AN:

52642

Other (OTH)

AF:

0.0635

AC:

AN:

1511

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

126

252

379

505

631

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0474

Hom.:

732

Bravo

AF:

0.0581

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.63

PhyloP100

0.48

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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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rs4503258

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