chr6-108677702-G-C

Position:

• chr6-108677702-G-C

Variant summary

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

The NM_001455.4(FOXO3):​c.*35-2125G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 151,858 control chromosomes in the GnomAD database, including 26,344 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 (26344 hom., cov: 31)
• Consequence: FOXO3 NM_001455.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.35

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.699 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXO3	NM_001455.4	c.*35-2125G>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.*35-2125G>C		intron_variant		1	NM_001455.4	ENSP00000385824	P1
FOXO3	ENST00000343882.10	c.*35-2125G>C		intron_variant		1		ENSP00000339527	P1
FOXO3	ENST00000540898.1	c.*35-2125G>C		intron_variant		1		ENSP00000446316

Frequencies

GnomAD3 genomes AF: 0.540 AC: 82000 AN: 151740 Hom.: 26345 Cov.: 31

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.814

Gnomad AMR AF: 0.639

Gnomad ASJ AF: 0.749

Gnomad EAS AF: 0.710

Gnomad SAS AF: 0.528

Gnomad FIN AF: 0.622

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.704

Gnomad OTH AF: 0.571

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

GnomAD4 genome AF: 0.540 AC: 82016 AN: 151858 Hom.: 26344 Cov.: 31 AF XY: 0.539 AC XY: 40005 AN XY: 74182

Gnomad4 AFR AF: 0.168

Gnomad4 AMR AF: 0.639

Gnomad4 ASJ AF: 0.749

Gnomad4 EAS AF: 0.709

Gnomad4 SAS AF: 0.529

Gnomad4 FIN AF: 0.622

Gnomad4 NFE AF: 0.704

Gnomad4 OTH AF: 0.573

Alfa AF: 0.467 Hom.: 1553

Bravo AF: 0.529

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.8
DANN	Benign	0.41

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: rs1935952; hg19: chr6-108998905;