6-108675760-G-T

Variant names:

• chr6-108675760-G-T
• rs3800229
• NM_001455.4:c.*35-4067G>T

Variant summary

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

The NM_001455.4(FOXO3):​c.*35-4067G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 152,060 control chromosomes in the GnomAD database, including 26,506 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 0.54 (26506 hom., cov: 32)
• Consequence: FOXO3 NM_001455.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0870
• Publications: 41 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.699 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXO3	NM_001455.4	MANE Select	c.*35-4067G>T		intron	N/A	NP_001446.1
	FOXO3	NM_201559.3		c.*35-4067G>T		intron	N/A	NP_963853.1
	FOXO3	NM_001415139.1		c.*35-4067G>T		intron	N/A	NP_001402068.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXO3	ENST00000406360.2	TSL:1 MANE Select	c.*35-4067G>T		intron	N/A	ENSP00000385824.1
	FOXO3	ENST00000343882.10	TSL:1	c.*35-4067G>T		intron	N/A	ENSP00000339527.6
	FOXO3	ENST00000540898.1	TSL:1	c.*35-4067G>T		intron	N/A	ENSP00000446316.1

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82726 AN: 151942 Hom.: 26507 Cov.: 32

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.813

Gnomad AMR AF: 0.640

Gnomad ASJ AF: 0.751

Gnomad EAS AF: 0.711

Gnomad SAS AF: 0.533

Gnomad FIN AF: 0.621

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.705

Gnomad OTH AF: 0.571

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

GnomAD4 genome AF: 0.544 AC: 82748 AN: 152060 Hom.: 26506 Cov.: 32 AF XY: 0.543 AC XY: 40383 AN XY: 74332

African (AFR) AF: 0.182 AC: 7565 AN: 41470

American (AMR) AF: 0.640 AC: 9776 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.751 AC: 2608 AN: 3472

East Asian (EAS) AF: 0.710 AC: 3668 AN: 5166

South Asian (SAS) AF: 0.534 AC: 2568 AN: 4812

European-Finnish (FIN) AF: 0.621 AC: 6558 AN: 10566

Middle Eastern (MID) AF: 0.541 AC: 158 AN: 292

European-Non Finnish (NFE) AF: 0.705 AC: 47893 AN: 67978

Other (OTH) AF: 0.573 AC: 1213 AN: 2116

Alfa AF: 0.652 Hom.: 102655

Bravo AF: 0.533

Asia WGS AF: 0.561 AC: 1950 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.4
DANN	Benign	0.42
PhyloP100		-0.087
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: rs3800229; hg19: chr6-108996963;