chr6-108613258-C-T

Position:

• chr6-108613258-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.622-50197C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 152,038 control chromosomes in the GnomAD database, including 25,124 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 0.53 (25124 hom., cov: 32)
• Consequence: FOXO3 NM_001455.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.347

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXO3	NM_001455.4	c.622-50197C>T		intron_variant		ENST00000406360.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXO3	ENST00000406360.2	c.622-50197C>T		intron_variant		1	NM_001455.4	P1
FOXO3	ENST00000343882.10	c.622-50197C>T		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80378 AN: 151920 Hom.: 25123 Cov.: 32

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.786

Gnomad AMR AF: 0.629

Gnomad ASJ AF: 0.734

Gnomad EAS AF: 0.693

Gnomad SAS AF: 0.510

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.685

Gnomad OTH AF: 0.556

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

GnomAD4 genome AF: 0.529 AC: 80399 AN: 152038 Hom.: 25124 Cov.: 32 AF XY: 0.529 AC XY: 39279 AN XY: 74304

Gnomad4 AFR AF: 0.172

Gnomad4 AMR AF: 0.629

Gnomad4 ASJ AF: 0.734

Gnomad4 EAS AF: 0.693

Gnomad4 SAS AF: 0.511

Gnomad4 FIN AF: 0.612

Gnomad4 NFE AF: 0.685

Gnomad4 OTH AF: 0.558

Alfa AF: 0.666 Hom.: 38536

Bravo AF: 0.518

Asia WGS AF: 0.542 AC: 1886 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.40
DANN	Benign	0.25
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2764264; hg19: chr6-108934461;