rs7762395

Variant names:

• chr6-108623904-G-A
• rs7762395
• NM_001455.4:c.622-39551G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-108623904-G-A
• chr6-108623904-G-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.622-39551G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 152,064 control chromosomes in the GnomAD database, including 2,659 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 0.18 (2659 hom., cov: 32)
• Consequence: FOXO3 NM_001455.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50
• Publications: 24 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.244 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.622-39551G>A		intron	N/A	NP_001446.1	O43524-1
	FOXO3	NM_201559.3		c.622-39551G>A		intron	N/A	NP_963853.1	O43524-1
	FOXO3	NM_001415139.1		c.121-39551G>A		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.622-39551G>A		intron	N/A	ENSP00000385824.1	O43524-1
	FOXO3	ENST00000343882.10	TSL:1	c.622-39551G>A		intron	N/A	ENSP00000339527.6	O43524-1
	FOXO3	ENST00000898147.1		c.622-39551G>A		intron	N/A	ENSP00000568206.1

Frequencies

GnomAD3 genomes AF: 0.178 AC: 26994 AN: 151946 Hom.: 2655 Cov.: 32

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.0890

Gnomad EAS AF: 0.0574

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.187

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

GnomAD4 genome AF: 0.178 AC: 27012 AN: 152064 Hom.: 2659 Cov.: 32 AF XY: 0.173 AC XY: 12858 AN XY: 74346

African (AFR) AF: 0.248 AC: 10300 AN: 41462

American (AMR) AF: 0.214 AC: 3273 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0890 AC: 307 AN: 3450

East Asian (EAS) AF: 0.0574 AC: 297 AN: 5178

South Asian (SAS) AF: 0.118 AC: 571 AN: 4822

European-Finnish (FIN) AF: 0.110 AC: 1161 AN: 10596

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.155 AC: 10555 AN: 67956

Other (OTH) AF: 0.185 AC: 391 AN: 2110

Alfa AF: 0.108 Hom.: 191

Bravo AF: 0.192

Asia WGS AF: 0.127 AC: 441 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.34
DANN	Benign	0.85
PhyloP100		-1.5
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: rs7762395; hg19: chr6-108945107; COSMIC: COSV59630243;