rs2802288

Variant names:

• chr6-108575012-A-G
• rs2802288
• NM_001455.4:c.621+13183A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-108575012-A-G
• chr6-108575012-A-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+13183A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.503 in 151,992 control chromosomes in the GnomAD database, including 21,387 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 0.50 (21387 hom., cov: 31)
• Consequence: FOXO3 NM_001455.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• Publications: 31 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXO3	NM_001455.4	c.621+13183A>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.621+13183A>G		intron_variant	Intron 1 of 2	1	NM_001455.4	ENSP00000385824.1
FOXO3	ENST00000343882.10	c.621+13183A>G		intron_variant	Intron 2 of 3	1		ENSP00000339527.6
ENSG00000294744	ENST00000725671.1	n.452+7463A>G		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.503 AC: 76418 AN: 151874 Hom.: 21380 Cov.: 31

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.742

Gnomad AMR AF: 0.586

Gnomad ASJ AF: 0.628

Gnomad EAS AF: 0.684

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.567

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.613

Gnomad OTH AF: 0.507

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

GnomAD4 genome AF: 0.503 AC: 76465 AN: 151992 Hom.: 21387 Cov.: 31 AF XY: 0.504 AC XY: 37468 AN XY: 74286

African (AFR) AF: 0.244 AC: 10135 AN: 41488

American (AMR) AF: 0.586 AC: 8953 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.628 AC: 2178 AN: 3466

East Asian (EAS) AF: 0.684 AC: 3533 AN: 5168

South Asian (SAS) AF: 0.456 AC: 2192 AN: 4812

European-Finnish (FIN) AF: 0.567 AC: 5970 AN: 10534

Middle Eastern (MID) AF: 0.438 AC: 128 AN: 292

European-Non Finnish (NFE) AF: 0.613 AC: 41630 AN: 67942

Other (OTH) AF: 0.509 AC: 1071 AN: 2106

Alfa AF: 0.578 Hom.: 19910

Bravo AF: 0.498

Asia WGS AF: 0.528 AC: 1838 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	0.094
DANN	Benign	0.43
PhyloP100		-1.2
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: rs2802288; hg19: chr6-108896215;