rs13220810

Variant names:

• chr6-108591998-T-C
• rs13220810
• NM_001455.4:c.621+30169T>C

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+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 NM_001455.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.454
• Publications: 25 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=-0.91).
• 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 rank	MANE	Protein	UniProt
FOXO3	NM_001455.4	c.621+30169T>C		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+30169T>C		intron_variant	Intron 1 of 2	1	NM_001455.4	ENSP00000385824.1
FOXO3	ENST00000343882.10	c.621+30169T>C		intron_variant	Intron 2 of 3	1		ENSP00000339527.6
ENSG00000294744	ENST00000725671.1	n.452+24449T>C		intron_variant	Intron 2 of 2

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

African (AFR) AF: 0.0440 AC: 1824 AN: 41428

American (AMR) AF: 0.189 AC: 2885 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 798 AN: 3462

East Asian (EAS) AF: 0.104 AC: 538 AN: 5170

South Asian (SAS) AF: 0.177 AC: 854 AN: 4822

European-Finnish (FIN) AF: 0.196 AC: 2066 AN: 10534

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.248 AC: 16875 AN: 67928

Other (OTH) AF: 0.170 AC: 359 AN: 2108

Alfa AF: 0.226 Hom.: 5753

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
PhyloP100		-0.45
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: rs13220810; hg19: chr6-108913201;