chr6-108652895-C-T

Variant names:

• chr6-108652895-C-T
• rs13217795
• NM_001455.4:c.622-10560C>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.622-10560C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 152,022 control chromosomes in the GnomAD database, including 26,563 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 0.56 (26563 hom., cov: 31)
• Consequence: FOXO3 NM_001455.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.169
• Publications: 49 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=-0.72).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXO3	NM_001455.4	c.622-10560C>T		intron_variant	Intron 1 of 2	ENST00000406360.2	NP_001446.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXO3	ENST00000406360.2	c.622-10560C>T		intron_variant	Intron 1 of 2	1	NM_001455.4	ENSP00000385824.1
FOXO3	ENST00000343882.10	c.622-10560C>T		intron_variant	Intron 2 of 3	1		ENSP00000339527.6

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84963 AN: 151904 Hom.: 26557 Cov.: 31

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.786

Gnomad AMR AF: 0.640

Gnomad ASJ AF: 0.741

Gnomad EAS AF: 0.694

Gnomad SAS AF: 0.529

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.694

Gnomad OTH AF: 0.574

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

GnomAD4 genome AF: 0.559 AC: 85010 AN: 152022 Hom.: 26563 Cov.: 31 AF XY: 0.558 AC XY: 41460 AN XY: 74292

African (AFR) AF: 0.260 AC: 10761 AN: 41448

American (AMR) AF: 0.640 AC: 9791 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.741 AC: 2571 AN: 3468

East Asian (EAS) AF: 0.694 AC: 3577 AN: 5156

South Asian (SAS) AF: 0.530 AC: 2551 AN: 4816

European-Finnish (FIN) AF: 0.614 AC: 6488 AN: 10568

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.694 AC: 47186 AN: 67956

Other (OTH) AF: 0.576 AC: 1215 AN: 2108

Alfa AF: 0.609 Hom.: 3742

Bravo AF: 0.550

Asia WGS AF: 0.557 AC: 1937 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	3.7
DANN	Benign	0.83
PhyloP100		0.17
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: rs13217795; hg19: chr6-108974098; COSMIC: COSV59631186; COSMIC: COSV59631186;