6-108613258-C-T

Variant names:

• chr6-108613258-C-T
• rs2764264
• NM_001455.4:c.622-50197C>T

Variant summary

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

The NM_001455.4(FOXO3):​c.622-50197C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 152,038 control chromosomes in the GnomAD database, including 25,124 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 0.53 (25124 hom., cov: 32)
• Consequence: FOXO3 NM_001455.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.347
• Publications: 42 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]

ENSG00000294744 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.68 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXO3	NM_001455.4	MANE Select	c.622-50197C>T		intron	N/A	NP_001446.1	O43524-1
	FOXO3	NM_201559.3		c.622-50197C>T		intron	N/A	NP_963853.1	O43524-1
	FOXO3	NM_001415139.1		c.121-50197C>T		intron	N/A	NP_001402068.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXO3	ENST00000406360.2	TSL:1 MANE Select	c.622-50197C>T		intron	N/A	ENSP00000385824.1	O43524-1
	FOXO3	ENST00000343882.10	TSL:1	c.622-50197C>T		intron	N/A	ENSP00000339527.6	O43524-1
	FOXO3	ENST00000898147.1		c.622-50197C>T		intron	N/A	ENSP00000568206.1

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80378 AN: 151920 Hom.: 25123 Cov.: 32

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.786

Gnomad AMR AF: 0.629

Gnomad ASJ AF: 0.734

Gnomad EAS AF: 0.693

Gnomad SAS AF: 0.510

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.685

Gnomad OTH AF: 0.556

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

GnomAD4 genome AF: 0.529 AC: 80399 AN: 152038 Hom.: 25124 Cov.: 32 AF XY: 0.529 AC XY: 39279 AN XY: 74304

African (AFR) AF: 0.172 AC: 7134 AN: 41482

American (AMR) AF: 0.629 AC: 9616 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.734 AC: 2547 AN: 3470

East Asian (EAS) AF: 0.693 AC: 3581 AN: 5170

South Asian (SAS) AF: 0.511 AC: 2462 AN: 4816

European-Finnish (FIN) AF: 0.612 AC: 6455 AN: 10546

Middle Eastern (MID) AF: 0.541 AC: 158 AN: 292

European-Non Finnish (NFE) AF: 0.685 AC: 46551 AN: 67958

Other (OTH) AF: 0.558 AC: 1180 AN: 2114

Alfa AF: 0.628 Hom.: 61470

Bravo AF: 0.518

Asia WGS AF: 0.542 AC: 1886 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.40
DANN	Benign	0.25
PhyloP100		-0.35
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2764264; hg19: chr6-108934461;