6-108677063-A-G

Variant names:

• chr6-108677063-A-G
• rs3800231
• NM_001455.4:c.*35-2764A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001455.4(FOXO3):​c.*35-2764A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 152,114 control chromosomes in the GnomAD database, including 26,519 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 (26519 hom., cov: 32)
• Consequence: FOXO3 NM_001455.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.515
• Publications: 22 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• 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 rank	MANE	Protein	UniProt
FOXO3	NM_001455.4	c.*35-2764A>G		intron_variant	Intron 2 of 2	ENST00000406360.2	NP_001446.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXO3	ENST00000406360.2	c.*35-2764A>G		intron_variant	Intron 2 of 2	1	NM_001455.4	ENSP00000385824.1
FOXO3	ENST00000343882.10	c.*35-2764A>G		intron_variant	Intron 3 of 3	1		ENSP00000339527.6
FOXO3	ENST00000540898.1	c.*35-2764A>G		intron_variant	Intron 2 of 2	1		ENSP00000446316.1

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82759 AN: 151996 Hom.: 26520 Cov.: 32

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.813

Gnomad AMR AF: 0.641

Gnomad ASJ AF: 0.751

Gnomad EAS AF: 0.710

Gnomad SAS AF: 0.532

Gnomad FIN AF: 0.621

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.705

Gnomad OTH AF: 0.571

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

GnomAD4 genome AF: 0.544 AC: 82781 AN: 152114 Hom.: 26519 Cov.: 32 AF XY: 0.543 AC XY: 40412 AN XY: 74356

African (AFR) AF: 0.182 AC: 7573 AN: 41504

American (AMR) AF: 0.641 AC: 9801 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.751 AC: 2608 AN: 3472

East Asian (EAS) AF: 0.710 AC: 3659 AN: 5156

South Asian (SAS) AF: 0.533 AC: 2571 AN: 4820

European-Finnish (FIN) AF: 0.621 AC: 6570 AN: 10576

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.705 AC: 47891 AN: 67974

Other (OTH) AF: 0.573 AC: 1208 AN: 2108

Alfa AF: 0.581 Hom.: 3632

Bravo AF: 0.533

Asia WGS AF: 0.561 AC: 1952 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.91
DANN	Benign	0.74
PhyloP100		-0.52
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3800231; hg19: chr6-108998266;