6-108567390-C-G

Variant names:

• chr6-108567390-C-G
• rs2253310
• NM_001455.4:c.621+5561C>G

Variant summary

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

The NM_001415146.1(FOXO3):​c.-199C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 152,036 control chromosomes in the GnomAD database, including 21,478 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 (21478 hom., cov: 31)
• Consequence: FOXO3 NM_001415146.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.560

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXO3	NM_001455.4	c.621+5561C>G		intron_variant	Intron 1 of 2	ENST00000406360.2	NP_001446.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXO3	ENST00000406360.2	c.621+5561C>G		intron_variant	Intron 1 of 2	1	NM_001455.4	ENSP00000385824.1
FOXO3	ENST00000343882.10	c.621+5561C>G		intron_variant	Intron 2 of 3	1		ENSP00000339527.6

Frequencies

GnomAD3 genomes AF: 0.505 AC: 76703 AN: 151918 Hom.: 21470 Cov.: 31

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.742

Gnomad AMR AF: 0.591

Gnomad ASJ AF: 0.628

Gnomad EAS AF: 0.686

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.566

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.613

Gnomad OTH AF: 0.513

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

GnomAD4 genome AF: 0.505 AC: 76753 AN: 152036 Hom.: 21478 Cov.: 31 AF XY: 0.506 AC XY: 37614 AN XY: 74294

Gnomad4 AFR AF: 0.249

Gnomad4 AMR AF: 0.591

Gnomad4 ASJ AF: 0.628

Gnomad4 EAS AF: 0.685

Gnomad4 SAS AF: 0.456

Gnomad4 FIN AF: 0.566

Gnomad4 NFE AF: 0.612

Gnomad4 OTH AF: 0.515

Alfa AF: 0.415 Hom.: 1301

Bravo AF: 0.500

Asia WGS AF: 0.528 AC: 1837 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.74
DANN	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs2253310; hg19: chr6-108888593;