rs9400239

Variant names:

• chr6-108656460-T-C
• rs9400239
• ENST00000540898.1:c.-118T>C

Your query was ambiguous. Multiple possible variants found:

• chr6-108656460-T-C
• chr6-108656460-T-G

Variant summary

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

The ENST00000540898.1(FOXO3):​c.-118T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.669 in 984,696 control chromosomes in the GnomAD database, including 226,859 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 0.55 (26201 hom., cov: 31)
  • Exomes 𝑓: 0.69 (200658 hom.)
• Consequence: FOXO3 ENST00000540898.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.39
• Publications: 111 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXO3	NM_001455.4	c.622-6995T>C		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	ENST00000540898.1	c.-118T>C		5_prime_UTR_variant	Exon 1 of 3	1		ENSP00000446316.1
FOXO3	ENST00000406360.2	c.622-6995T>C		intron_variant	Intron 1 of 2	1	NM_001455.4	ENSP00000385824.1
FOXO3	ENST00000343882.10	c.622-6995T>C		intron_variant	Intron 2 of 3	1		ENSP00000339527.6

Frequencies

GnomAD3 genomes AF: 0.552 AC: 83889 AN: 151944 Hom.: 26194 Cov.: 31

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.785

Gnomad AMR AF: 0.638

Gnomad ASJ AF: 0.739

Gnomad EAS AF: 0.697

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.693

Gnomad OTH AF: 0.570

GnomAD4 exome AF: 0.690 AC: 574485 AN: 832634 Hom.: 200658 Cov.: 31 AF XY: 0.690 AC XY: 265187 AN XY: 384502

African (AFR) AF: 0.209 AC: 3301 AN: 15774

American (AMR) AF: 0.635 AC: 625 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.746 AC: 3842 AN: 5148

East Asian (EAS) AF: 0.713 AC: 2584 AN: 3626

South Asian (SAS) AF: 0.523 AC: 8592 AN: 16442

European-Finnish (FIN) AF: 0.620 AC: 170 AN: 274

Middle Eastern (MID) AF: 0.581 AC: 942 AN: 1620

European-Non Finnish (NFE) AF: 0.705 AC: 536751 AN: 761482

Other (OTH) AF: 0.648 AC: 17678 AN: 27284

GnomAD4 genome AF: 0.552 AC: 83936 AN: 152062 Hom.: 26201 Cov.: 31 AF XY: 0.551 AC XY: 40992 AN XY: 74338

African (AFR) AF: 0.238 AC: 9888 AN: 41484

American (AMR) AF: 0.638 AC: 9747 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.739 AC: 2565 AN: 3472

East Asian (EAS) AF: 0.696 AC: 3599 AN: 5168

South Asian (SAS) AF: 0.519 AC: 2501 AN: 4818

European-Finnish (FIN) AF: 0.614 AC: 6480 AN: 10560

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.693 AC: 47085 AN: 67962

Other (OTH) AF: 0.573 AC: 1207 AN: 2108

Alfa AF: 0.654 Hom.: 54404

Bravo AF: 0.543

Asia WGS AF: 0.551 AC: 1916 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	13
DANN	Benign	0.69
PhyloP100		1.4
PromoterAI		-0.055	Neutral
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: rs9400239; hg19: chr6-108977663;