6-108630452-T-C

Position:

• chr6-108630452-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXO3	NM_001455.4	c.622-33003T>C		intron_variant		ENST00000406360.2	NP_001446.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXO3	ENST00000406360.2	c.622-33003T>C		intron_variant		1	NM_001455.4	ENSP00000385824	P1
FOXO3	ENST00000343882.10	c.622-33003T>C		intron_variant		1		ENSP00000339527	P1

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

Gnomad4 AFR AF: 0.377

Gnomad4 AMR AF: 0.242

Gnomad4 ASJ AF: 0.125

Gnomad4 EAS AF: 0.0880

Gnomad4 SAS AF: 0.167

Gnomad4 FIN AF: 0.118

Gnomad4 NFE AF: 0.163

Gnomad4 OTH AF: 0.235

Alfa AF: 0.172 Hom.: 3221

Bravo AF: 0.243

Asia WGS AF: 0.170 AC: 589 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.0
DANN	Benign	0.80

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

Publications

LitVar

Other links and lift over

dbSNP: rs9285397; hg19: chr6-108951655;