rs2802292

Positions:

• chr6-108587315-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001455.4(FOXO3):​c.621+25486G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.503 in 151,818 control chromosomes in the GnomAD database, including 21,333 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.50 (21333 hom., cov: 30)
• Consequence: FOXO3 NM_001455.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.02

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 6-108587315-G-T is Benign according to our data. Variant chr6-108587315-G-T is described in ClinVar as [Benign]. Clinvar id is 1269978.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXO3	NM_001455.4	c.621+25486G>T		intron_variant		ENST00000406360.2	NP_001446.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXO3	ENST00000406360.2	c.621+25486G>T		intron_variant		1	NM_001455.4	ENSP00000385824	P1
FOXO3	ENST00000343882.10	c.621+25486G>T		intron_variant		1		ENSP00000339527	P1

Frequencies

GnomAD3 genomes AF: 0.503 AC: 76266 AN: 151700 Hom.: 21326 Cov.: 30

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.742

Gnomad AMR AF: 0.586

Gnomad ASJ AF: 0.628

Gnomad EAS AF: 0.683

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.566

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.506

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

GnomAD4 genome AF: 0.503 AC: 76313 AN: 151818 Hom.: 21333 Cov.: 30 AF XY: 0.504 AC XY: 37371 AN XY: 74154

Gnomad4 AFR AF: 0.243

Gnomad4 AMR AF: 0.586

Gnomad4 ASJ AF: 0.628

Gnomad4 EAS AF: 0.683

Gnomad4 SAS AF: 0.456

Gnomad4 FIN AF: 0.566

Gnomad4 NFE AF: 0.612

Gnomad4 OTH AF: 0.508

Alfa AF: 0.564 Hom.: 7750

Bravo AF: 0.497

Asia WGS AF: 0.528 AC: 1838 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 18, 2020

This variant is associated with the following publications: (PMID: 29733381) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.20
DANN	Benign	0.48

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

Publications

LitVar

Other links and lift over

dbSNP: rs2802292; hg19: chr6-108908518;