rs17532874

Variant names:

• chr6-108610801-T-C
• rs17532874
• NM_001455.4:c.621+48972T>C

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+48972T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.042 in 152,308 control chromosomes in the GnomAD database, including 203 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 0.042 (203 hom., cov: 32)
• Consequence: FOXO3 NM_001455.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.344
• Publications: 3 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0595 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXO3	NM_001455.4	MANE Select	c.621+48972T>C		intron	N/A	NP_001446.1
	FOXO3	NM_201559.3		c.621+48972T>C		intron	N/A	NP_963853.1
	FOXO3	NM_001415139.1		c.120+48658T>C		intron	N/A	NP_001402068.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXO3	ENST00000406360.2	TSL:1 MANE Select	c.621+48972T>C		intron	N/A	ENSP00000385824.1
	FOXO3	ENST00000343882.10	TSL:1	c.621+48972T>C		intron	N/A	ENSP00000339527.6
	ENSG00000294744	ENST00000725671.1		n.453-28692T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0421 AC: 6402 AN: 152190 Hom.: 204 Cov.: 32

Gnomad AFR AF: 0.0101

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0431

Gnomad ASJ AF: 0.0761

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0590

Gnomad FIN AF: 0.0432

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0611

Gnomad OTH AF: 0.0526

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

GnomAD4 genome AF: 0.0420 AC: 6398 AN: 152308 Hom.: 203 Cov.: 32 AF XY: 0.0412 AC XY: 3071 AN XY: 74482

African (AFR) AF: 0.0101 AC: 419 AN: 41568

American (AMR) AF: 0.0430 AC: 658 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0761 AC: 264 AN: 3470

East Asian (EAS) AF: 0.00173 AC: 9 AN: 5196

South Asian (SAS) AF: 0.0587 AC: 283 AN: 4824

European-Finnish (FIN) AF: 0.0432 AC: 458 AN: 10610

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0611 AC: 4156 AN: 68026

Other (OTH) AF: 0.0520 AC: 110 AN: 2114

Alfa AF: 0.0507 Hom.: 35

Bravo AF: 0.0395

Asia WGS AF: 0.0280 AC: 98 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	0.82
PhyloP100		-0.34
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: rs17532874; hg19: chr6-108932004;