rs9285397

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001455.4(FOXO3):​c.622-33003T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 152,058 control chromosomes in the GnomAD database, including 4,610 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 0.22 ( 4610 hom., cov: 31)

Consequence

FOXO3
NM_001455.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.491
Variant links:
Genes affected
FOXO3 (HGNC:3821): (forkhead box O3) This gene belongs to the forkhead family of transcription factors which are characterized by a distinct forkhead domain. This gene likely functions as a trigger for apoptosis through expression of genes necessary for cell death. Translocation of this gene with the MLL gene is associated with secondary acute leukemia. Alternatively spliced transcript variants encoding the same protein have been observed. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FOXO3NM_001455.4 linkuse as main transcriptc.622-33003T>C intron_variant ENST00000406360.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FOXO3ENST00000406360.2 linkuse as main transcriptc.622-33003T>C intron_variant 1 NM_001455.4 P1O43524-1
FOXO3ENST00000343882.10 linkuse as main transcriptc.622-33003T>C intron_variant 1 P1O43524-1

Frequencies

GnomAD3 genomes
AF:
0.224
AC:
33990
AN:
151940
Hom.:
4604
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.378
Gnomad AMI
AF:
0.0855
Gnomad AMR
AF:
0.242
Gnomad ASJ
AF:
0.125
Gnomad EAS
AF:
0.0880
Gnomad SAS
AF:
0.167
Gnomad FIN
AF:
0.118
Gnomad MID
AF:
0.320
Gnomad NFE
AF:
0.163
Gnomad OTH
AF:
0.237
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.224
AC:
34018
AN:
152058
Hom.:
4610
Cov.:
31
AF XY:
0.219
AC XY:
16255
AN XY:
74344
show subpopulations
Gnomad4 AFR
AF:
0.377
Gnomad4 AMR
AF:
0.242
Gnomad4 ASJ
AF:
0.125
Gnomad4 EAS
AF:
0.0880
Gnomad4 SAS
AF:
0.167
Gnomad4 FIN
AF:
0.118
Gnomad4 NFE
AF:
0.163
Gnomad4 OTH
AF:
0.235
Alfa
AF:
0.172
Hom.:
3221
Bravo
AF:
0.243
Asia WGS
AF:
0.170
AC:
589
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
CADD
Benign
5.0
DANN
Benign
0.80

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs9285397; hg19: chr6-108951655; API