chr6-108595370-T-C

Variant names:

• chr6-108595370-T-C
• rs9480865
• NM_001455.4:c.621+33541T>C

Variant summary

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

The NM_001455.4(FOXO3):​c.621+33541T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 152,214 control chromosomes in the GnomAD database, including 2,798 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 (2798 hom., cov: 31)
• Consequence: FOXO3 NM_001455.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.230
• Publications: 25 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.248 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.621+33541T>C		intron	N/A	NP_001446.1
	FOXO3	NM_201559.3		c.621+33541T>C		intron	N/A	NP_963853.1
	FOXO3	NM_001415139.1		c.120+33227T>C		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.621+33541T>C		intron	N/A	ENSP00000385824.1
	FOXO3	ENST00000343882.10	TSL:1	c.621+33541T>C		intron	N/A	ENSP00000339527.6
	ENSG00000294744	ENST00000725671.1		n.452+27821T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27666 AN: 152098 Hom.: 2793 Cov.: 31

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.0861

Gnomad EAS AF: 0.0590

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.190

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

GnomAD4 genome AF: 0.182 AC: 27685 AN: 152214 Hom.: 2798 Cov.: 31 AF XY: 0.177 AC XY: 13167 AN XY: 74428

African (AFR) AF: 0.252 AC: 10472 AN: 41498

American (AMR) AF: 0.219 AC: 3354 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0861 AC: 299 AN: 3472

East Asian (EAS) AF: 0.0590 AC: 306 AN: 5190

South Asian (SAS) AF: 0.121 AC: 582 AN: 4828

European-Finnish (FIN) AF: 0.112 AC: 1192 AN: 10612

Middle Eastern (MID) AF: 0.274 AC: 80 AN: 292

European-Non Finnish (NFE) AF: 0.161 AC: 10924 AN: 68004

Other (OTH) AF: 0.189 AC: 399 AN: 2116

Alfa AF: 0.162 Hom.: 1062

Bravo AF: 0.196

Asia WGS AF: 0.121 AC: 420 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	10
DANN	Benign	0.49
PhyloP100		-0.23
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: rs9480865; hg19: chr6-108916573; COSMIC: COSV59627028;