rs12206094

Positions:

• chr6-108584997-C-T

Variant summary

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

The NM_001455.4(FOXO3):​c.621+23168C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 141,584 control chromosomes in the GnomAD database, including 6,542 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 0.31 (6542 hom., cov: 25)
• Consequence: FOXO3 NM_001455.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0900

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXO3	NM_001455.4	c.621+23168C>T		intron_variant		ENST00000406360.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXO3	ENST00000406360.2	c.621+23168C>T		intron_variant		1	NM_001455.4	P1
FOXO3	ENST00000343882.10	c.621+23168C>T		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.306 AC: 43246 AN: 141488 Hom.: 6545 Cov.: 25

Gnomad AFR AF: 0.358

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.382

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.318

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

GnomAD4 genome AF: 0.306 AC: 43256 AN: 141584 Hom.: 6542 Cov.: 25 AF XY: 0.304 AC XY: 20641 AN XY: 67806

Gnomad4 AFR AF: 0.357

Gnomad4 AMR AF: 0.309

Gnomad4 ASJ AF: 0.230

Gnomad4 EAS AF: 0.239

Gnomad4 SAS AF: 0.222

Gnomad4 FIN AF: 0.299

Gnomad4 NFE AF: 0.289

Gnomad4 OTH AF: 0.317

Alfa AF: 0.286 Hom.: 3365

Bravo AF: 0.303

Asia WGS AF: 0.241 AC: 835 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.8
DANN	Benign	0.84

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: rs12206094; hg19: chr6-108906200; COSMIC: COSV59627018;