NM_001455.4:c.*35-2077C>T

Variant names:

• chr6-108677750-C-T
• rs3800232
• NM_001455.4:c.*35-2077C>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.*35-2077C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 152,016 control chromosomes in the GnomAD database, including 1,845 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 0.15 (1845 hom., cov: 31)
• Consequence: FOXO3 NM_001455.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0740
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.27 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.*35-2077C>T		intron	N/A	NP_001446.1	O43524-1
	FOXO3	NM_201559.3		c.*35-2077C>T		intron	N/A	NP_963853.1	O43524-1
	FOXO3	NM_001415139.1		c.*35-2077C>T		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.*35-2077C>T		intron	N/A	ENSP00000385824.1	O43524-1
	FOXO3	ENST00000343882.10	TSL:1	c.*35-2077C>T		intron	N/A	ENSP00000339527.6	O43524-1
	FOXO3	ENST00000540898.1	TSL:1	c.*35-2077C>T		intron	N/A	ENSP00000446316.1	O43524-2

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22473 AN: 151898 Hom.: 1848 Cov.: 31

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.0993

Gnomad AMR AF: 0.0893

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.132

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

GnomAD4 genome AF: 0.148 AC: 22476 AN: 152016 Hom.: 1845 Cov.: 31 AF XY: 0.155 AC XY: 11502 AN XY: 74282

African (AFR) AF: 0.156 AC: 6455 AN: 41454

American (AMR) AF: 0.0891 AC: 1360 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 435 AN: 3470

East Asian (EAS) AF: 0.205 AC: 1058 AN: 5168

South Asian (SAS) AF: 0.282 AC: 1360 AN: 4818

European-Finnish (FIN) AF: 0.261 AC: 2749 AN: 10546

Middle Eastern (MID) AF: 0.130 AC: 38 AN: 292

European-Non Finnish (NFE) AF: 0.127 AC: 8651 AN: 67994

Other (OTH) AF: 0.133 AC: 280 AN: 2106

Alfa AF: 0.125 Hom.: 1228

Bravo AF: 0.130

Asia WGS AF: 0.248 AC: 861 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.9
DANN	Benign	0.57
PhyloP100		0.074
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: rs3800232; hg19: chr6-108998953;