rs12206094

Variant names:

• chr6-108584997-C-T
• rs12206094
• NM_001455.4:c.621+23168C>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.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
• Publications: 40 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.352 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXO3	NM_001455.4	MANE Select	c.621+23168C>T		intron	N/A	NP_001446.1	O43524-1
	FOXO3	NM_201559.3		c.621+23168C>T		intron	N/A	NP_963853.1	O43524-1
	FOXO3	NM_001415139.1		c.120+22854C>T		intron	N/A	NP_001402068.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXO3	ENST00000406360.2	TSL:1 MANE Select	c.621+23168C>T		intron	N/A	ENSP00000385824.1	O43524-1
	FOXO3	ENST00000343882.10	TSL:1	c.621+23168C>T		intron	N/A	ENSP00000339527.6	O43524-1
	FOXO3	ENST00000898147.1		c.621+23168C>T		intron	N/A	ENSP00000568206.1

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

African (AFR) AF: 0.357 AC: 13883 AN: 38890

American (AMR) AF: 0.309 AC: 4197 AN: 13576

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 780 AN: 3384

East Asian (EAS) AF: 0.239 AC: 1094 AN: 4580

South Asian (SAS) AF: 0.222 AC: 963 AN: 4334

European-Finnish (FIN) AF: 0.299 AC: 2360 AN: 7892

Middle Eastern (MID) AF: 0.369 AC: 99 AN: 268

European-Non Finnish (NFE) AF: 0.289 AC: 19042 AN: 65816

Other (OTH) AF: 0.317 AC: 627 AN: 1976

Alfa AF: 0.285 Hom.: 3682

Bravo AF: 0.303

Asia WGS AF: 0.241 AC: 835 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.8
DANN	Benign	0.84
PhyloP100		0.090
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: rs12206094; hg19: chr6-108906200; COSMIC: COSV59627018;