6-108656460-T-C

Position:

• chr6-108656460-T-C

Variant summary

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

The ENST00000540898.1(FOXO3):​c.-118T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.669 in 984,696 control chromosomes in the GnomAD database, including 226,859 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 0.55 (26201 hom., cov: 31)
  • Exomes 𝑓: 0.69 (200658 hom.)
• Consequence: FOXO3 ENST00000540898.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.39

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXO3	NM_001455.4	c.622-6995T>C		intron_variant		ENST00000406360.2	NP_001446.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXO3	ENST00000540898.1	c.-118T>C		5_prime_UTR_variant	1/3	1		ENSP00000446316
FOXO3	ENST00000406360.2	c.622-6995T>C		intron_variant		1	NM_001455.4	ENSP00000385824	P1
FOXO3	ENST00000343882.10	c.622-6995T>C		intron_variant		1		ENSP00000339527	P1

Frequencies

GnomAD3 genomes AF: 0.552 AC: 83889 AN: 151944 Hom.: 26194 Cov.: 31

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.785

Gnomad AMR AF: 0.638

Gnomad ASJ AF: 0.739

Gnomad EAS AF: 0.697

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.693

Gnomad OTH AF: 0.570

GnomAD4 exome AF: 0.690 AC: 574485 AN: 832634 Hom.: 200658 Cov.: 31 AF XY: 0.690 AC XY: 265187 AN XY: 384502

Gnomad4 AFR exome AF: 0.209

Gnomad4 AMR exome AF: 0.635

Gnomad4 ASJ exome AF: 0.746

Gnomad4 EAS exome AF: 0.713

Gnomad4 SAS exome AF: 0.523

Gnomad4 FIN exome AF: 0.620

Gnomad4 NFE exome AF: 0.705

Gnomad4 OTH exome AF: 0.648

GnomAD4 genome AF: 0.552 AC: 83936 AN: 152062 Hom.: 26201 Cov.: 31 AF XY: 0.551 AC XY: 40992 AN XY: 74338

Gnomad4 AFR AF: 0.238

Gnomad4 AMR AF: 0.638

Gnomad4 ASJ AF: 0.739

Gnomad4 EAS AF: 0.696

Gnomad4 SAS AF: 0.519

Gnomad4 FIN AF: 0.614

Gnomad4 NFE AF: 0.693

Gnomad4 OTH AF: 0.573

Alfa AF: 0.628 Hom.: 9649

Bravo AF: 0.543

Asia WGS AF: 0.551 AC: 1916 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	13
DANN	Benign	0.69

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: rs9400239; hg19: chr6-108977663;