6-108678084-A-G

Variant names:

• chr6-108678084-A-G
• rs1935949
• NM_001455.4:c.*35-1743A>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.*35-1743A>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 152,064 control chromosomes in the GnomAD database, including 26,517 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 (26517 hom., cov: 31)
• Consequence: FOXO3 NM_001455.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.00
• Publications: 32 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.699 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001455.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXO3	NM_001455.4	MANE Select	c.*35-1743A>G		intron	N/A	NP_001446.1
	FOXO3	NM_201559.3		c.*35-1743A>G		intron	N/A	NP_963853.1
	FOXO3	NM_001415139.1		c.*35-1743A>G		intron	N/A	NP_001402068.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXO3	ENST00000406360.2	TSL:1 MANE Select	c.*35-1743A>G		intron	N/A	ENSP00000385824.1
	FOXO3	ENST00000343882.10	TSL:1	c.*35-1743A>G		intron	N/A	ENSP00000339527.6
	FOXO3	ENST00000540898.1	TSL:1	c.*35-1743A>G		intron	N/A	ENSP00000446316.1

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82716 AN: 151946 Hom.: 26518 Cov.: 31

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: 0.537

Gnomad FIN AF: 0.620

Gnomad MID AF: 0.544

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: 82738 AN: 152064 Hom.: 26517 Cov.: 31 AF XY: 0.543 AC XY: 40385 AN XY: 74326

African (AFR) AF: 0.182 AC: 7552 AN: 41492

American (AMR) AF: 0.641 AC: 9788 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.751 AC: 2607 AN: 3470

East Asian (EAS) AF: 0.709 AC: 3665 AN: 5166

South Asian (SAS) AF: 0.538 AC: 2594 AN: 4824

European-Finnish (FIN) AF: 0.620 AC: 6529 AN: 10534

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.704 AC: 47891 AN: 67982

Other (OTH) AF: 0.573 AC: 1211 AN: 2112

Alfa AF: 0.658 Hom.: 55663

Bravo AF: 0.533

Asia WGS AF: 0.563 AC: 1959 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.016
DANN	Benign	0.56
PhyloP100		-5.0
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: rs1935949; hg19: chr6-108999287;