chr6-108677702-G-C

Variant names:

• chr6-108677702-G-C
• rs1935952
• NM_001455.4:c.*35-2125G>C

Variant summary

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

The ENST00000406360.2(FOXO3):​c.*35-2125G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 151,858 control chromosomes in the GnomAD database, including 26,344 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 (26344 hom., cov: 31)
• Consequence: FOXO3 ENST00000406360.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.35
• Publications: 14 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=-0.83).
• 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: ENST00000406360.2. 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.*35-2125G>C		intron	N/A	NP_001446.1
	FOXO3	NM_201559.3		c.*35-2125G>C		intron	N/A	NP_963853.1
	FOXO3	NM_001415139.1		c.*35-2125G>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.*35-2125G>C		intron	N/A	ENSP00000385824.1
	FOXO3	ENST00000343882.10	TSL:1	c.*35-2125G>C		intron	N/A	ENSP00000339527.6
	FOXO3	ENST00000540898.1	TSL:1	c.*35-2125G>C		intron	N/A	ENSP00000446316.1

Frequencies

GnomAD3 genomes AF: 0.540 AC: 82000 AN: 151740 Hom.: 26345 Cov.: 31

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.814

Gnomad AMR AF: 0.639

Gnomad ASJ AF: 0.749

Gnomad EAS AF: 0.710

Gnomad SAS AF: 0.528

Gnomad FIN AF: 0.622

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.704

Gnomad OTH AF: 0.571

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

GnomAD4 genome AF: 0.540 AC: 82016 AN: 151858 Hom.: 26344 Cov.: 31 AF XY: 0.539 AC XY: 40005 AN XY: 74182

African (AFR) AF: 0.168 AC: 6977 AN: 41408

American (AMR) AF: 0.639 AC: 9761 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.749 AC: 2599 AN: 3468

East Asian (EAS) AF: 0.709 AC: 3661 AN: 5160

South Asian (SAS) AF: 0.529 AC: 2550 AN: 4816

European-Finnish (FIN) AF: 0.622 AC: 6547 AN: 10522

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.704 AC: 47819 AN: 67914

Other (OTH) AF: 0.573 AC: 1205 AN: 2102

Alfa AF: 0.467 Hom.: 1553

Bravo AF: 0.529

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.8
DANN	Benign	0.41
PhyloP100		1.3
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: rs1935952; hg19: chr6-108998905;