6-108576183-A-G

Position:

• chr6-108576183-A-G

Variant summary

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

The NM_001455.4(FOXO3):​c.621+14354A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 152,214 control chromosomes in the GnomAD database, including 1,460 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 0.13 (1460 hom., cov: 32)
• Consequence: FOXO3 NM_001455.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.26

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=-0.64).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXO3	NM_001455.4	c.621+14354A>G		intron_variant		ENST00000406360.2	NP_001446.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXO3	ENST00000406360.2	c.621+14354A>G		intron_variant		1	NM_001455.4	ENSP00000385824.1
FOXO3	ENST00000343882.10	c.621+14354A>G		intron_variant		1		ENSP00000339527.6

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19555 AN: 152094 Hom.: 1456 Cov.: 32

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.0242

Gnomad AMR AF: 0.0900

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.0705

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.120

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

GnomAD4 genome AF: 0.129 AC: 19577 AN: 152214 Hom.: 1460 Cov.: 32 AF XY: 0.132 AC XY: 9820 AN XY: 74424

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.0899

Gnomad4 ASJ AF: 0.110

Gnomad4 EAS AF: 0.0707

Gnomad4 SAS AF: 0.270

Gnomad4 FIN AF: 0.164

Gnomad4 NFE AF: 0.101

Gnomad4 OTH AF: 0.119

Alfa AF: 0.0890 Hom.: 189

Bravo AF: 0.120

Asia WGS AF: 0.172 AC: 599 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	9.4
DANN	Benign	0.68

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: rs2883881; hg19: chr6-108897386;