rs3800230

Variant names:

• chr6-108676925-T-G
• rs3800230
• NM_001455.4:c.*35-2902T>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.*35-2902T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 152,232 control chromosomes in the GnomAD database, including 1,854 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 0.15 (1854 hom., cov: 33)
• Consequence: FOXO3 NM_001455.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.52
• Publications: 19 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=-0.68).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXO3	NM_001455.4	c.*35-2902T>G		intron_variant	Intron 2 of 2	ENST00000406360.2	NP_001446.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXO3	ENST00000406360.2	c.*35-2902T>G		intron_variant	Intron 2 of 2	1	NM_001455.4	ENSP00000385824.1
FOXO3	ENST00000343882.10	c.*35-2902T>G		intron_variant	Intron 3 of 3	1		ENSP00000339527.6
FOXO3	ENST00000540898.1	c.*35-2902T>G		intron_variant	Intron 2 of 2	1		ENSP00000446316.1

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22546 AN: 152114 Hom.: 1857 Cov.: 33

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.0893

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.134

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

GnomAD4 genome AF: 0.148 AC: 22549 AN: 152232 Hom.: 1854 Cov.: 33 AF XY: 0.155 AC XY: 11543 AN XY: 74410

African (AFR) AF: 0.156 AC: 6489 AN: 41546

American (AMR) AF: 0.0891 AC: 1363 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 434 AN: 3470

East Asian (EAS) AF: 0.204 AC: 1057 AN: 5174

South Asian (SAS) AF: 0.288 AC: 1391 AN: 4822

European-Finnish (FIN) AF: 0.259 AC: 2743 AN: 10580

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8656 AN: 68024

Other (OTH) AF: 0.134 AC: 283 AN: 2110

Alfa AF: 0.127 Hom.: 4065

Bravo AF: 0.131

Asia WGS AF: 0.250 AC: 869 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	12
DANN	Benign	0.84
PhyloP100		1.5
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: rs3800230; hg19: chr6-108998128;