chr13-40564252-C-T

Position:

• chr13-40564252-C-T

Variant summary

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

The NM_002015.4(FOXO1):​c.631-3392G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0737 in 151,070 control chromosomes in the GnomAD database, including 505 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 0.074 (505 hom., cov: 31)
• Consequence: FOXO1 NM_002015.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.328

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXO1	NM_002015.4	c.631-3392G>A		intron_variant		ENST00000379561.6	NP_002006.2
FOXO1	XM_011535010.3	c.-1645G>A		5_prime_UTR_variant	1/3		XP_011533312.1
FOXO1	XM_011535008.3	c.88-3392G>A		intron_variant			XP_011533310.1
FOXO1	XM_047430204.1	c.-81-3392G>A		intron_variant			XP_047286160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXO1	ENST00000379561.6	c.631-3392G>A		intron_variant		1	NM_002015.4	ENSP00000368880.4
ENSG00000288542	ENST00000636651.2	n.108-3392G>A		intron_variant		5
FOXO1	ENST00000655267.1	n.334-1490G>A		intron_variant
FOXO1	ENST00000660760.1	n.398-3392G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0737 AC: 11125 AN: 150956 Hom.: 503 Cov.: 31

Gnomad AFR AF: 0.0746

Gnomad AMI AF: 0.0780

Gnomad AMR AF: 0.0678

Gnomad ASJ AF: 0.0912

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.0291

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0649

Gnomad OTH AF: 0.0886

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

GnomAD4 genome AF: 0.0737 AC: 11129 AN: 151070 Hom.: 505 Cov.: 31 AF XY: 0.0731 AC XY: 5388 AN XY: 73732

Gnomad4 AFR AF: 0.0745

Gnomad4 AMR AF: 0.0677

Gnomad4 ASJ AF: 0.0912

Gnomad4 EAS AF: 0.238

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.0291

Gnomad4 NFE AF: 0.0649

Gnomad4 OTH AF: 0.0891

Alfa AF: 0.0628 Hom.: 47

Bravo AF: 0.0765

Asia WGS AF: 0.145 AC: 506 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.2
DANN	Benign	0.54

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: rs2701858; hg19: chr13-41138389;