rs12202049

Variant names:

• chr6-108647474-G-C
• rs12202049
• NM_001455.4:c.622-15981G>C

Your query was ambiguous. Multiple possible variants found:

• chr6-108647474-G-C
• chr6-108647474-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.622-15981G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0968 in 152,216 control chromosomes in the GnomAD database, including 746 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 0.097 (746 hom., cov: 32)
• Consequence: FOXO3 NM_001455.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13
• Publications: 7 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001455.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXO3	NM_001455.4	MANE Select	c.622-15981G>C		intron	N/A	NP_001446.1	O43524-1
	FOXO3	NM_201559.3		c.622-15981G>C		intron	N/A	NP_963853.1	O43524-1
	FOXO3	NM_001415139.1		c.121-15981G>C		intron	N/A	NP_001402068.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXO3	ENST00000406360.2	TSL:1 MANE Select	c.622-15981G>C		intron	N/A	ENSP00000385824.1	O43524-1
	FOXO3	ENST00000343882.10	TSL:1	c.622-15981G>C		intron	N/A	ENSP00000339527.6	O43524-1
	FOXO3	ENST00000898147.1		c.622-15981G>C		intron	N/A	ENSP00000568206.1

Frequencies

GnomAD3 genomes AF: 0.0969 AC: 14731 AN: 152098 Hom.: 747 Cov.: 32

Gnomad AFR AF: 0.0774

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.0623

Gnomad ASJ AF: 0.0896

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.0772

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.0981

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

GnomAD4 genome AF: 0.0968 AC: 14730 AN: 152216 Hom.: 746 Cov.: 32 AF XY: 0.0984 AC XY: 7322 AN XY: 74398

African (AFR) AF: 0.0771 AC: 3204 AN: 41554

American (AMR) AF: 0.0622 AC: 951 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0896 AC: 311 AN: 3472

East Asian (EAS) AF: 0.153 AC: 791 AN: 5178

South Asian (SAS) AF: 0.0781 AC: 377 AN: 4828

European-Finnish (FIN) AF: 0.149 AC: 1573 AN: 10564

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7189 AN: 68010

Other (OTH) AF: 0.0985 AC: 208 AN: 2112

Alfa AF: 0.0570 Hom.: 64

Bravo AF: 0.0881

Asia WGS AF: 0.111 AC: 387 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	7.9
DANN	Benign	0.50
PhyloP100		1.1
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: rs12202049; hg19: chr6-108968677;