rs2153960

Positions:

• chr6-108666981-G-A
• chr6-108666981-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001455.4(FOXO3):​c.*34+2092G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.534 in 152,002 control chromosomes in the GnomAD database, including 25,771 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 0.53 (25771 hom., cov: 31)
• Consequence: FOXO3 NM_001455.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.21

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXO3	NM_001455.4	c.*34+2092G>A		intron_variant		ENST00000406360.2	NP_001446.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXO3	ENST00000406360.2	c.*34+2092G>A		intron_variant		1	NM_001455.4	ENSP00000385824	P1
FOXO3	ENST00000343882.10	c.*34+2092G>A		intron_variant		1		ENSP00000339527	P1
FOXO3	ENST00000540898.1	c.*34+2092G>A		intron_variant		1		ENSP00000446316

Frequencies

GnomAD3 genomes AF: 0.535 AC: 81199 AN: 151884 Hom.: 25772 Cov.: 31

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.810

Gnomad AMR AF: 0.630

Gnomad ASJ AF: 0.731

Gnomad EAS AF: 0.695

Gnomad SAS AF: 0.519

Gnomad FIN AF: 0.616

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.697

Gnomad OTH AF: 0.557

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

GnomAD4 genome AF: 0.534 AC: 81214 AN: 152002 Hom.: 25771 Cov.: 31 AF XY: 0.533 AC XY: 39622 AN XY: 74274

Gnomad4 AFR AF: 0.169

Gnomad4 AMR AF: 0.630

Gnomad4 ASJ AF: 0.731

Gnomad4 EAS AF: 0.694

Gnomad4 SAS AF: 0.520

Gnomad4 FIN AF: 0.616

Gnomad4 NFE AF: 0.697

Gnomad4 OTH AF: 0.559

Alfa AF: 0.676 Hom.: 59516

Bravo AF: 0.522

Asia WGS AF: 0.544 AC: 1894 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	14
DANN	Benign	0.67

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: rs2153960; hg19: chr6-108988184;