NM_001455.4:c.622-33003T>C

Variant names:

• chr6-108630452-T-C
• rs9285397
• NM_001455.4:c.622-33003T>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.622-33003T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 152,058 control chromosomes in the GnomAD database, including 4,610 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 0.22 (4610 hom., cov: 31)
• Consequence: FOXO3 NM_001455.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.491
• Publications: 12 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.372 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.622-33003T>C		intron	N/A	NP_001446.1
	FOXO3	NM_201559.3		c.622-33003T>C		intron	N/A	NP_963853.1
	FOXO3	NM_001415139.1		c.121-33003T>C		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.622-33003T>C		intron	N/A	ENSP00000385824.1
	FOXO3	ENST00000343882.10	TSL:1	c.622-33003T>C		intron	N/A	ENSP00000339527.6
	ENSG00000294744	ENST00000725671.1		n.453-9041T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.224 AC: 33990 AN: 151940 Hom.: 4604 Cov.: 31

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.0855

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.0880

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.237

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

GnomAD4 genome AF: 0.224 AC: 34018 AN: 152058 Hom.: 4610 Cov.: 31 AF XY: 0.219 AC XY: 16255 AN XY: 74344

African (AFR) AF: 0.377 AC: 15636 AN: 41438

American (AMR) AF: 0.242 AC: 3695 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 434 AN: 3466

East Asian (EAS) AF: 0.0880 AC: 455 AN: 5172

South Asian (SAS) AF: 0.167 AC: 808 AN: 4830

European-Finnish (FIN) AF: 0.118 AC: 1250 AN: 10612

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.163 AC: 11068 AN: 67958

Other (OTH) AF: 0.235 AC: 496 AN: 2112

Alfa AF: 0.183 Hom.: 5292

Bravo AF: 0.243

Asia WGS AF: 0.170 AC: 589 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.0
DANN	Benign	0.80
PhyloP100		-0.49
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: rs9285397; hg19: chr6-108951655;