rs12200646

Variant names:

• chr6-108576458-G-A
• rs12200646
• NM_001455.4:c.621+14629G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-108576458-G-A
• chr6-108576458-G-T

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+14629G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 152,216 control chromosomes in the GnomAD database, including 900 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 0.11 (900 hom., cov: 33)
• Consequence: FOXO3 NM_001455.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.619
• Publications: 6 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXO3	NM_001455.4	c.621+14629G>A		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+14629G>A		intron_variant	Intron 1 of 2	1	NM_001455.4	ENSP00000385824.1
FOXO3	ENST00000343882.10	c.621+14629G>A		intron_variant	Intron 2 of 3	1		ENSP00000339527.6
ENSG00000294744	ENST00000725671.1	n.452+8909G>A		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16248 AN: 152098 Hom.: 901 Cov.: 33

Gnomad AFR AF: 0.0801

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.0711

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.0864

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.113

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

GnomAD4 genome AF: 0.107 AC: 16245 AN: 152216 Hom.: 900 Cov.: 33 AF XY: 0.107 AC XY: 7994 AN XY: 74438

African (AFR) AF: 0.0799 AC: 3318 AN: 41534

American (AMR) AF: 0.0710 AC: 1086 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 487 AN: 3472

East Asian (EAS) AF: 0.158 AC: 820 AN: 5190

South Asian (SAS) AF: 0.0869 AC: 419 AN: 4824

European-Finnish (FIN) AF: 0.151 AC: 1599 AN: 10588

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.120 AC: 8149 AN: 67988

Other (OTH) AF: 0.114 AC: 242 AN: 2114

Alfa AF: 0.0646 Hom.: 82

Bravo AF: 0.0982

Asia WGS AF: 0.117 AC: 409 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.4
DANN	Benign	0.56
PhyloP100		0.62
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: rs12200646; hg19: chr6-108897661;