rs12207868

Variant names:

• chr6-108643682-A-G
• rs12207868
• NM_001455.4:c.622-19773A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001455.4(FOXO3):​c.622-19773A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.097 in 152,184 control chromosomes in the GnomAD database, including 748 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 0.097 (748 hom., cov: 32)
• Consequence: FOXO3 NM_001455.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.273
• Publications: 14 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXO3	NM_001455.4	c.622-19773A>G		intron_variant	Intron 1 of 2	ENST00000406360.2	NP_001446.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXO3	ENST00000406360.2	c.622-19773A>G		intron_variant	Intron 1 of 2	1	NM_001455.4	ENSP00000385824.1
FOXO3	ENST00000343882.10	c.622-19773A>G		intron_variant	Intron 2 of 3	1		ENSP00000339527.6

Frequencies

GnomAD3 genomes AF: 0.0971 AC: 14763 AN: 152066 Hom.: 749 Cov.: 32

Gnomad AFR AF: 0.0774

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.0623

Gnomad ASJ AF: 0.0893

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.0774

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.0955

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.0986

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

GnomAD4 genome AF: 0.0970 AC: 14762 AN: 152184 Hom.: 748 Cov.: 32 AF XY: 0.0985 AC XY: 7330 AN XY: 74382

African (AFR) AF: 0.0772 AC: 3206 AN: 41532

American (AMR) AF: 0.0622 AC: 951 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0893 AC: 310 AN: 3470

East Asian (EAS) AF: 0.152 AC: 784 AN: 5162

South Asian (SAS) AF: 0.0783 AC: 378 AN: 4828

European-Finnish (FIN) AF: 0.149 AC: 1580 AN: 10588

Middle Eastern (MID) AF: 0.0788 AC: 23 AN: 292

European-Non Finnish (NFE) AF: 0.106 AC: 7218 AN: 68000

Other (OTH) AF: 0.0990 AC: 209 AN: 2112

Alfa AF: 0.100 Hom.: 583

Bravo AF: 0.0883

Asia WGS AF: 0.111 AC: 386 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.4
DANN	Benign	0.59
PhyloP100		0.27
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: rs12207868; hg19: chr6-108964885;