NM_001455.4:c.621+22648G>A

Variant names:

• chr6-108584477-G-A
• rs2802290
• NM_001455.4:c.621+22648G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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]

ENSG00000294744 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
FOXO3	NM_001455.4	c.621+22648G>A		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+22648G>A		intron_variant	Intron 1 of 2	1	NM_001455.4	ENSP00000385824.1
FOXO3	ENST00000343882.10	c.621+22648G>A		intron_variant	Intron 2 of 3	1		ENSP00000339527.6
ENSG00000294744	ENST00000725671.1	n.452+16928G>A		intron_variant	Intron 2 of 2

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

African (AFR) AF: 0.244 AC: 10139 AN: 41508

American (AMR) AF: 0.586 AC: 8951 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.628 AC: 2182 AN: 3472

East Asian (EAS) AF: 0.683 AC: 3522 AN: 5158

South Asian (SAS) AF: 0.457 AC: 2202 AN: 4818

European-Finnish (FIN) AF: 0.566 AC: 5968 AN: 10546

Middle Eastern (MID) AF: 0.438 AC: 128 AN: 292

European-Non Finnish (NFE) AF: 0.612 AC: 41622 AN: 67966

Other (OTH) AF: 0.509 AC: 1076 AN: 2114

Alfa AF: 0.597 Hom.: 14008

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
PhyloP100		0.89
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2802290; hg19: chr6-108905680;