rs2802292

Variant names:

• chr6-108587315-G-T
• rs2802292
• NM_001455.4:c.621+25486G>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001455.4(FOXO3):​c.621+25486G>T 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 151,818 control chromosomes in the GnomAD database, including 21,333 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.50 (21333 hom., cov: 30)
• Consequence: FOXO3 NM_001455.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.02
• Publications: 123 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 6-108587315-G-T is Benign according to our data. Variant chr6-108587315-G-T is described in ClinVar as Benign. ClinVar VariationId is 1269978.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001455.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXO3	NM_001455.4	MANE Select	c.621+25486G>T		intron	N/A	NP_001446.1	O43524-1
	FOXO3	NM_201559.3		c.621+25486G>T		intron	N/A	NP_963853.1	O43524-1
	FOXO3	NM_001415139.1		c.120+25172G>T		intron	N/A	NP_001402068.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXO3	ENST00000406360.2	TSL:1 MANE Select	c.621+25486G>T		intron	N/A	ENSP00000385824.1	O43524-1
	FOXO3	ENST00000343882.10	TSL:1	c.621+25486G>T		intron	N/A	ENSP00000339527.6	O43524-1
	FOXO3	ENST00000898147.1		c.621+25486G>T		intron	N/A	ENSP00000568206.1

Frequencies

GnomAD3 genomes AF: 0.503 AC: 76266 AN: 151700 Hom.: 21326 Cov.: 30

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.742

Gnomad AMR AF: 0.586

Gnomad ASJ AF: 0.628

Gnomad EAS AF: 0.683

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.566

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.506

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

GnomAD4 genome AF: 0.503 AC: 76313 AN: 151818 Hom.: 21333 Cov.: 30 AF XY: 0.504 AC XY: 37371 AN XY: 74154

African (AFR) AF: 0.243 AC: 10072 AN: 41386

American (AMR) AF: 0.586 AC: 8936 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.628 AC: 2179 AN: 3470

East Asian (EAS) AF: 0.683 AC: 3515 AN: 5146

South Asian (SAS) AF: 0.456 AC: 2201 AN: 4822

European-Finnish (FIN) AF: 0.566 AC: 5964 AN: 10534

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.612 AC: 41573 AN: 67910

Other (OTH) AF: 0.508 AC: 1066 AN: 2098

Alfa AF: 0.561 Hom.: 9545

Bravo AF: 0.497

Asia WGS AF: 0.528 AC: 1838 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.20
DANN	Benign	0.48
PhyloP100		-1.0
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: rs2802292; hg19: chr6-108908518;