rs9398172

Variant names:

• chr6-108673623-G-A
• rs9398172
• NM_001455.4:c.*35-6204G>A

Variant summary

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

The NM_001455.4(FOXO3):​c.*35-6204G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 152,134 control chromosomes in the GnomAD database, including 26,528 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 0.55 (26528 hom., cov: 32)
• Consequence: FOXO3 NM_001455.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.483
• Publications: 16 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.699 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXO3	NM_001455.4	c.*35-6204G>A		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.*35-6204G>A		intron_variant	Intron 2 of 2	1	NM_001455.4	ENSP00000385824.1
FOXO3	ENST00000343882.10	c.*35-6204G>A		intron_variant	Intron 3 of 3	1		ENSP00000339527.6
FOXO3	ENST00000540898.1	c.*35-6204G>A		intron_variant	Intron 2 of 2	1		ENSP00000446316.1

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82929 AN: 152016 Hom.: 26529 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.813

Gnomad AMR AF: 0.640

Gnomad ASJ AF: 0.752

Gnomad EAS AF: 0.709

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.621

Gnomad MID AF: 0.548

Gnomad NFE AF: 0.704

Gnomad OTH AF: 0.572

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

GnomAD4 genome AF: 0.545 AC: 82950 AN: 152134 Hom.: 26528 Cov.: 32 AF XY: 0.545 AC XY: 40503 AN XY: 74368

African (AFR) AF: 0.187 AC: 7739 AN: 41480

American (AMR) AF: 0.640 AC: 9778 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.752 AC: 2607 AN: 3468

East Asian (EAS) AF: 0.708 AC: 3661 AN: 5170

South Asian (SAS) AF: 0.536 AC: 2591 AN: 4830

European-Finnish (FIN) AF: 0.621 AC: 6568 AN: 10580

Middle Eastern (MID) AF: 0.548 AC: 160 AN: 292

European-Non Finnish (NFE) AF: 0.704 AC: 47892 AN: 68008

Other (OTH) AF: 0.574 AC: 1213 AN: 2114

Alfa AF: 0.648 Hom.: 93605

Bravo AF: 0.535

Asia WGS AF: 0.562 AC: 1956 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.88
DANN	Benign	0.61
PhyloP100		-0.48
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: rs9398172; hg19: chr6-108994826;