6-108610801-T-C

Position:

• chr6-108610801-T-C

Variant summary

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

The NM_001455.4(FOXO3):​c.621+48972T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.042 in 152,308 control chromosomes in the GnomAD database, including 203 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 0.042 (203 hom., cov: 32)
• Consequence: FOXO3 NM_001455.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.344

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0595 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXO3	NM_001455.4	c.621+48972T>C		intron_variant		ENST00000406360.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXO3	ENST00000406360.2	c.621+48972T>C		intron_variant		1	NM_001455.4	P1
FOXO3	ENST00000343882.10	c.621+48972T>C		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.0421 AC: 6402 AN: 152190 Hom.: 204 Cov.: 32

Gnomad AFR AF: 0.0101

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0431

Gnomad ASJ AF: 0.0761

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0590

Gnomad FIN AF: 0.0432

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0611

Gnomad OTH AF: 0.0526

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

GnomAD4 genome AF: 0.0420 AC: 6398 AN: 152308 Hom.: 203 Cov.: 32 AF XY: 0.0412 AC XY: 3071 AN XY: 74482

Gnomad4 AFR AF: 0.0101

Gnomad4 AMR AF: 0.0430

Gnomad4 ASJ AF: 0.0761

Gnomad4 EAS AF: 0.00173

Gnomad4 SAS AF: 0.0587

Gnomad4 FIN AF: 0.0432

Gnomad4 NFE AF: 0.0611

Gnomad4 OTH AF: 0.0520

Alfa AF: 0.0507 Hom.: 35

Bravo AF: 0.0395

Asia WGS AF: 0.0280 AC: 98 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.9
DANN	Benign	0.82

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: rs17532874; hg19: chr6-108932004;