6-108680839-C-T

Position:

• chr6-108680839-C-T

Variant summary

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

The NM_001455.4(FOXO3):​c.*1047C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 151,358 control chromosomes in the GnomAD database, including 26,034 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 0.54 (26011 hom., cov: 31)
  • Exomes 𝑓: 0.56 (23 hom.)
• Consequence: FOXO3 NM_001455.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.605

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXO3	NM_001455.4	c.*1047C>T		3_prime_UTR_variant	3/3	ENST00000406360.2	NP_001446.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXO3	ENST00000406360.2	c.*1047C>T		3_prime_UTR_variant	3/3	1	NM_001455.4	ENSP00000385824.1
FOXO3	ENST00000343882.10	c.*1047C>T		3_prime_UTR_variant	4/4	1		ENSP00000339527.6

Frequencies

GnomAD3 genomes AF: 0.539 AC: 81417 AN: 151094 Hom.: 26013 Cov.: 31

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.813

Gnomad AMR AF: 0.637

Gnomad ASJ AF: 0.747

Gnomad EAS AF: 0.710

Gnomad SAS AF: 0.522

Gnomad FIN AF: 0.618

Gnomad MID AF: 0.542

Gnomad NFE AF: 0.702

Gnomad OTH AF: 0.565

GnomAD4 exome AF: 0.556 AC: 90 AN: 162 Hom.: 23 Cov.: 0 AF XY: 0.477 AC XY: 42 AN XY: 88

Gnomad4 FIN exome AF: 0.558

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.539 AC: 81430 AN: 151196 Hom.: 26011 Cov.: 31 AF XY: 0.537 AC XY: 39653 AN XY: 73808

Gnomad4 AFR AF: 0.170

Gnomad4 AMR AF: 0.637

Gnomad4 ASJ AF: 0.747

Gnomad4 EAS AF: 0.710

Gnomad4 SAS AF: 0.523

Gnomad4 FIN AF: 0.618

Gnomad4 NFE AF: 0.702

Gnomad4 OTH AF: 0.567

Alfa AF: 0.604 Hom.: 7840

Bravo AF: 0.529

Asia WGS AF: 0.553 AC: 1925 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	8.7
DANN	Benign	0.53

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: rs4945816; hg19: chr6-109002042;