rs2802290

Positions:

• chr6-108584477-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001455.4(FOXO3):​c.621+22648G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.503 in 152,062 control chromosomes in the GnomAD database, including 21,379 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 0.50 (21379 hom., cov: 32)
• Consequence: FOXO3 NM_001455.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.894

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXO3	NM_001455.4	c.621+22648G>A		intron_variant		ENST00000406360.2	NP_001446.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXO3	ENST00000406360.2	c.621+22648G>A		intron_variant		1	NM_001455.4	ENSP00000385824.1
FOXO3	ENST00000343882.10	c.621+22648G>A		intron_variant		1		ENSP00000339527.6

Frequencies

GnomAD3 genomes AF: 0.503 AC: 76420 AN: 151944 Hom.: 21372 Cov.: 32

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.742

Gnomad AMR AF: 0.586

Gnomad ASJ AF: 0.628

Gnomad EAS AF: 0.683

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.566

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.507

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.503 AC: 76467 AN: 152062 Hom.: 21379 Cov.: 32 AF XY: 0.504 AC XY: 37471 AN XY: 74312

Gnomad4 AFR AF: 0.244

Gnomad4 AMR AF: 0.586

Gnomad4 ASJ AF: 0.628

Gnomad4 EAS AF: 0.683

Gnomad4 SAS AF: 0.457

Gnomad4 FIN AF: 0.566

Gnomad4 NFE AF: 0.612

Gnomad4 OTH AF: 0.509

Alfa AF: 0.586 Hom.: 8389

Bravo AF: 0.497

Asia WGS AF: 0.528 AC: 1838 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	15
DANN	Benign	0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs2802290; hg19: chr6-108905680;