rs9486913

chr6-108639637-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001455.4(FOXO3):c.622-23818C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 883,824 control chromosomes in the GnomAD database, including 13,881 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 0.19 (3277 hom., cov: 32)
  • Exomes 𝑓: 0.18 (10604 hom.)
• Consequence: FOXO3 NM_001455.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXO3	NM_001455.4	c.622-23818C>G		intron_variant		ENST00000406360.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXO3	ENST00000406360.2	c.622-23818C>G		intron_variant		1	NM_001455.4	P1
FOXO3	ENST00000343882.10	c.622-23818C>G		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29608 AN: 151890 Hom.: 3274 Cov.: 32

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.0869

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.209

GnomAD4 exome AF: 0.175 AC: 128236 AN: 731816 Hom.: 10604 Cov.: 10 AF XY: 0.174 AC XY: 59299 AN XY: 339846

Gnomad4 AFR exome AF: 0.309

Gnomad4 AMR exome AF: 0.273

Gnomad4 ASJ exome AF: 0.113

Gnomad4 EAS exome AF: 0.0894

Gnomad4 SAS exome AF: 0.192

Gnomad4 FIN exome AF: 0.143

Gnomad4 NFE exome AF: 0.172

Gnomad4 OTH exome AF: 0.184

GnomAD4 genome AF: 0.195 AC: 29624 AN: 152008 Hom.: 3277 Cov.: 32 AF XY: 0.191 AC XY: 14197 AN XY: 74324

Gnomad4 AFR AF: 0.290

Gnomad4 AMR AF: 0.224

Gnomad4 ASJ AF: 0.112

Gnomad4 EAS AF: 0.0869

Gnomad4 SAS AF: 0.167

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.207

Alfa AF: 0.176 Hom.: 312

Bravo AF: 0.209

Asia WGS AF: 0.164 AC: 568 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.22
Dann	Benign	0.54

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: rs9486913; hg19: chr6-108960840; COSMIC: COSV59627056;