rs13220810

Positions:

• chr6-108591998-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000406360.2(FOXO3):​c.621+30169T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 151,924 control chromosomes in the GnomAD database, including 2,908 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 0.17 (2908 hom., cov: 32)
• Consequence: FOXO3 ENST00000406360.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.454

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXO3	NM_001455.4	c.621+30169T>C		intron_variant		ENST00000406360.2	NP_001446.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXO3	ENST00000406360.2	c.621+30169T>C		intron_variant		1	NM_001455.4	ENSP00000385824	P1
FOXO3	ENST00000343882.10	c.621+30169T>C		intron_variant		1		ENSP00000339527	P1

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26532 AN: 151806 Hom.: 2906 Cov.: 32

Gnomad AFR AF: 0.0442

Gnomad AMI AF: 0.320

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.172

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

GnomAD4 genome AF: 0.175 AC: 26533 AN: 151924 Hom.: 2908 Cov.: 32 AF XY: 0.171 AC XY: 12706 AN XY: 74248

Gnomad4 AFR AF: 0.0440

Gnomad4 AMR AF: 0.189

Gnomad4 ASJ AF: 0.231

Gnomad4 EAS AF: 0.104

Gnomad4 SAS AF: 0.177

Gnomad4 FIN AF: 0.196

Gnomad4 NFE AF: 0.248

Gnomad4 OTH AF: 0.170

Alfa AF: 0.231 Hom.: 4730

Bravo AF: 0.171

Asia WGS AF: 0.125 AC: 436 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.48

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

Publications

LitVar

Other links and lift over

dbSNP: rs13220810; hg19: chr6-108913201;