rs9480867

Variant names:

• chr6-108654443-G-A
• rs9480867
• NM_001455.4:c.622-9012G>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.622-9012G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 151,942 control chromosomes in the GnomAD database, including 3,141 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 0.19 (3141 hom., cov: 32)
• Consequence: FOXO3 NM_001455.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.00
• Publications: 10 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXO3	NM_001455.4	c.622-9012G>A		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.622-9012G>A		intron_variant	Intron 1 of 2	1	NM_001455.4	ENSP00000385824.1
FOXO3	ENST00000343882.10	c.622-9012G>A		intron_variant	Intron 2 of 3	1		ENSP00000339527.6

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29035 AN: 151822 Hom.: 3138 Cov.: 32

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.0846

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.0873

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.303

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.205

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

GnomAD4 genome AF: 0.191 AC: 29050 AN: 151942 Hom.: 3141 Cov.: 32 AF XY: 0.187 AC XY: 13904 AN XY: 74276

African (AFR) AF: 0.278 AC: 11481 AN: 41372

American (AMR) AF: 0.223 AC: 3411 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 389 AN: 3472

East Asian (EAS) AF: 0.0873 AC: 452 AN: 5178

South Asian (SAS) AF: 0.167 AC: 801 AN: 4808

European-Finnish (FIN) AF: 0.114 AC: 1200 AN: 10554

Middle Eastern (MID) AF: 0.315 AC: 92 AN: 292

European-Non Finnish (NFE) AF: 0.158 AC: 10718 AN: 67976

Other (OTH) AF: 0.204 AC: 429 AN: 2108

Alfa AF: 0.179 Hom.: 1011

Bravo AF: 0.205

Asia WGS AF: 0.163 AC: 565 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.4
DANN	Benign	0.42
PhyloP100		1.0
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: rs9480867; hg19: chr6-108975646; COSMIC: COSV59627074; COSMIC: COSV59627074;