chr6-108675350-T-C

Variant names:

• chr6-108675350-T-C
• rs3778588
• NM_001455.4:c.*35-4477T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001455.4(FOXO3):​c.*35-4477T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.733 in 151,964 control chromosomes in the GnomAD database, including 43,129 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 0.73 (43129 hom., cov: 30)
• Consequence: FOXO3 NM_001455.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27
• Publications: 8 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.893 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.*35-4477T>C		intron	N/A	NP_001446.1	O43524-1
	FOXO3	NM_201559.3		c.*35-4477T>C		intron	N/A	NP_963853.1	O43524-1
	FOXO3	NM_001415139.1		c.*35-4477T>C		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.*35-4477T>C		intron	N/A	ENSP00000385824.1	O43524-1
	FOXO3	ENST00000343882.10	TSL:1	c.*35-4477T>C		intron	N/A	ENSP00000339527.6	O43524-1
	FOXO3	ENST00000540898.1	TSL:1	c.*35-4477T>C		intron	N/A	ENSP00000446316.1	O43524-2

Frequencies

GnomAD3 genomes AF: 0.733 AC: 111365 AN: 151846 Hom.: 43118 Cov.: 30

Gnomad AFR AF: 0.466

Gnomad AMI AF: 0.916

Gnomad AMR AF: 0.750

Gnomad ASJ AF: 0.878

Gnomad EAS AF: 0.914

Gnomad SAS AF: 0.831

Gnomad FIN AF: 0.882

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.838

Gnomad OTH AF: 0.734

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

GnomAD4 genome AF: 0.733 AC: 111406 AN: 151964 Hom.: 43129 Cov.: 30 AF XY: 0.738 AC XY: 54825 AN XY: 74262

African (AFR) AF: 0.466 AC: 19299 AN: 41396

American (AMR) AF: 0.750 AC: 11453 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.878 AC: 3045 AN: 3470

East Asian (EAS) AF: 0.914 AC: 4726 AN: 5168

South Asian (SAS) AF: 0.832 AC: 3998 AN: 4808

European-Finnish (FIN) AF: 0.882 AC: 9331 AN: 10574

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.838 AC: 56969 AN: 67968

Other (OTH) AF: 0.736 AC: 1548 AN: 2102

Alfa AF: 0.802 Hom.: 47188

Bravo AF: 0.710

Asia WGS AF: 0.822 AC: 2857 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.57
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3778588; hg19: chr6-108996553;