chr6-108647474-G-C

Position:

• chr6-108647474-G-C

Variant summary

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

The ENST00000406360.2(FOXO3):​c.622-15981G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0968 in 152,216 control chromosomes in the GnomAD database, including 746 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 0.097 (746 hom., cov: 32)
• Consequence: FOXO3 ENST00000406360.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13

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=-0.61).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXO3	NM_001455.4	c.622-15981G>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.622-15981G>C		intron_variant		1	NM_001455.4	ENSP00000385824	P1
FOXO3	ENST00000343882.10	c.622-15981G>C		intron_variant		1		ENSP00000339527	P1

Frequencies

GnomAD3 genomes AF: 0.0969 AC: 14731 AN: 152098 Hom.: 747 Cov.: 32

Gnomad AFR AF: 0.0774

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.0623

Gnomad ASJ AF: 0.0896

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.0772

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.0981

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

GnomAD4 genome AF: 0.0968 AC: 14730 AN: 152216 Hom.: 746 Cov.: 32 AF XY: 0.0984 AC XY: 7322 AN XY: 74398

Gnomad4 AFR AF: 0.0771

Gnomad4 AMR AF: 0.0622

Gnomad4 ASJ AF: 0.0896

Gnomad4 EAS AF: 0.153

Gnomad4 SAS AF: 0.0781

Gnomad4 FIN AF: 0.149

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.0985

Alfa AF: 0.0570 Hom.: 64

Bravo AF: 0.0881

Asia WGS AF: 0.111 AC: 387 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	7.9
DANN	Benign	0.50

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: rs12202049; hg19: chr6-108968677;