6-108682118-T-C

Position:

• chr6-108682118-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001455.4(FOXO3):​c.*2326T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 152,522 control chromosomes in the GnomAD database, including 26,452 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.54 (26381 hom., cov: 32)
  • Exomes 𝑓: 0.63 (71 hom.)
• Consequence: FOXO3 NM_001455.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.552

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 6-108682118-T-C is Benign according to our data. Variant chr6-108682118-T-C is described in ClinVar as [Benign]. Clinvar id is 1272154.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXO3	NM_001455.4	c.*2326T>C		3_prime_UTR_variant	3/3	ENST00000406360.2	NP_001446.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXO3	ENST00000406360.2	c.*2326T>C		3_prime_UTR_variant	3/3	1	NM_001455.4	ENSP00000385824.1
FOXO3	ENST00000343882.10	c.*2326T>C		3_prime_UTR_variant	4/4	1		ENSP00000339527.6

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82188 AN: 152006 Hom.: 26382 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.813

Gnomad AMR AF: 0.639

Gnomad ASJ AF: 0.750

Gnomad EAS AF: 0.711

Gnomad SAS AF: 0.530

Gnomad FIN AF: 0.622

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.704

Gnomad OTH AF: 0.568

GnomAD4 exome AF: 0.628 AC: 250 AN: 398 Hom.: 71 Cov.: 0 AF XY: 0.633 AC XY: 152 AN XY: 240

Gnomad4 FIN exome AF: 0.630

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.540 AC: 82204 AN: 152124 Hom.: 26381 Cov.: 32 AF XY: 0.540 AC XY: 40125 AN XY: 74356

Gnomad4 AFR AF: 0.171

Gnomad4 AMR AF: 0.639

Gnomad4 ASJ AF: 0.750

Gnomad4 EAS AF: 0.710

Gnomad4 SAS AF: 0.531

Gnomad4 FIN AF: 0.622

Gnomad4 NFE AF: 0.704

Gnomad4 OTH AF: 0.570

Alfa AF: 0.600 Hom.: 8210

Bravo AF: 0.529

Asia WGS AF: 0.558 AC: 1942 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 15, 2020

This variant is associated with the following publications: (PMID: 25060657) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.8
DANN	Benign	0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Publications

LitVar

Other links and lift over

dbSNP: rs4946936; hg19: chr6-109003321; COSMIC: COSV59626116; COSMIC: COSV59626116;