rs12212067

Positions:

• chr6-108659993-T-G

Variant summary

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

The NM_001455.4(FOXO3):​c.622-3462T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 152,096 control chromosomes in the GnomAD database, including 1,528 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 0.13 (1528 hom., cov: 32)
• Consequence: FOXO3 NM_001455.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXO3	NM_001455.4	c.622-3462T>G		intron_variant		ENST00000406360.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXO3	ENST00000406360.2	c.622-3462T>G		intron_variant		1	NM_001455.4	P1
FOXO3	ENST00000343882.10	c.622-3462T>G		intron_variant		1		P1
FOXO3	ENST00000540898.1	c.-40+3455T>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20457 AN: 151980 Hom.: 1528 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.0870

Gnomad AMR AF: 0.0796

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.0873

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.123

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

GnomAD4 genome AF: 0.135 AC: 20476 AN: 152096 Hom.: 1528 Cov.: 32 AF XY: 0.135 AC XY: 10029 AN XY: 74340

Gnomad4 AFR AF: 0.201

Gnomad4 AMR AF: 0.0795

Gnomad4 ASJ AF: 0.109

Gnomad4 EAS AF: 0.153

Gnomad4 SAS AF: 0.0880

Gnomad4 FIN AF: 0.147

Gnomad4 NFE AF: 0.109

Gnomad4 OTH AF: 0.124

Alfa AF: 0.130 Hom.: 221

Bravo AF: 0.132

Asia WGS AF: 0.122 AC: 424 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.22
DANN	Benign	0.54

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: rs12212067; hg19: chr6-108981196;