13-40558943-A-G

Position:

• chr13-40558943-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002015.4(FOXO1):​c.*106T>C variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.204 in 395,628 control chromosomes in the GnomAD database, including 8,867 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 0.18 (2778 hom., cov: 30)
  • Exomes 𝑓: 0.22 (6089 hom.)
• Consequence: FOXO1 NM_002015.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.73

Genes affected

FOXO1 (HGNC:3819): (forkhead box O1) This gene belongs to the forkhead family of transcription factors which are characterized by a distinct forkhead domain. The specific function of this gene has not yet been determined; however, it may play a role in myogenic growth and differentiation. Translocation of this gene with PAX3 has been associated with alveolar rhabdomyosarcoma. [provided by RefSeq, Jul 2008]

ENSG00000288542 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXO1	NM_002015.4	c.*106T>C		3_prime_UTR_variant	3/3	ENST00000379561.6	NP_002006.2
FOXO1	XM_011535008.3	c.*106T>C		3_prime_UTR_variant	3/3		XP_011533310.1
FOXO1	XM_011535010.3	c.*106T>C		3_prime_UTR_variant	3/3		XP_011533312.1
FOXO1	XM_047430204.1	c.*106T>C		3_prime_UTR_variant	3/3		XP_047286160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXO1	ENST00000379561	c.*106T>C		3_prime_UTR_variant	3/3	1	NM_002015.4	ENSP00000368880.4
ENSG00000288542	ENST00000636651.2	n.1459+566T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27322 AN: 149000 Hom.: 2776 Cov.: 30

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.175

GnomAD4 exome AF: 0.216 AC: 53360 AN: 246538 Hom.: 6089 Cov.: 0 AF XY: 0.219 AC XY: 27357 AN XY: 124958

Gnomad4 AFR exome AF: 0.0909

Gnomad4 AMR exome AF: 0.153

Gnomad4 ASJ exome AF: 0.178

Gnomad4 EAS exome AF: 0.142

Gnomad4 SAS exome AF: 0.184

Gnomad4 FIN exome AF: 0.226

Gnomad4 NFE exome AF: 0.238

Gnomad4 OTH exome AF: 0.207

GnomAD4 genome AF: 0.183 AC: 27319 AN: 149090 Hom.: 2778 Cov.: 30 AF XY: 0.179 AC XY: 12992 AN XY: 72690

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.171

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.178

Gnomad4 FIN AF: 0.204

Gnomad4 NFE AF: 0.242

Gnomad4 OTH AF: 0.174

Alfa AF: 0.220 Hom.: 807

Bravo AF: 0.173

Asia WGS AF: 0.151 AC: 522 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	14
DANN	Benign	0.70

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: rs3751437; hg19: chr13-41133080;