6-108576183-A-G

Variant names:

• chr6-108576183-A-G
• rs2883881
• NM_001455.4:c.621+14354A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001455.4(FOXO3):​c.621+14354A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 152,214 control chromosomes in the GnomAD database, including 1,460 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 (1460 hom., cov: 32)
• Consequence: FOXO3 NM_001455.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.26
• Publications: 10 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]

ENSG00000294744 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXO3	NM_001455.4	c.621+14354A>G		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.621+14354A>G		intron_variant	Intron 1 of 2	1	NM_001455.4	ENSP00000385824.1
FOXO3	ENST00000343882.10	c.621+14354A>G		intron_variant	Intron 2 of 3	1		ENSP00000339527.6
ENSG00000294744	ENST00000725671.1	n.452+8634A>G		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19555 AN: 152094 Hom.: 1456 Cov.: 32

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.0242

Gnomad AMR AF: 0.0900

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.0705

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.120

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

GnomAD4 genome AF: 0.129 AC: 19577 AN: 152214 Hom.: 1460 Cov.: 32 AF XY: 0.132 AC XY: 9820 AN XY: 74424

African (AFR) AF: 0.175 AC: 7249 AN: 41504

American (AMR) AF: 0.0899 AC: 1376 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 380 AN: 3470

East Asian (EAS) AF: 0.0707 AC: 367 AN: 5190

South Asian (SAS) AF: 0.270 AC: 1304 AN: 4826

European-Finnish (FIN) AF: 0.164 AC: 1743 AN: 10596

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.101 AC: 6841 AN: 68008

Other (OTH) AF: 0.119 AC: 251 AN: 2114

Alfa AF: 0.0987 Hom.: 358

Bravo AF: 0.120

Asia WGS AF: 0.172 AC: 599 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	9.4
DANN	Benign	0.68
PhyloP100		1.3
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: rs2883881; hg19: chr6-108897386;