chr13-40564252-C-T

Variant names:

• chr13-40564252-C-T
• rs2701858
• NM_002015.4:c.631-3392G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
FOXO1	NM_002015.4	c.631-3392G>A		intron_variant	Intron 1 of 2	ENST00000379561.6	NP_002006.2
FOXO1	XM_011535010.3	c.-1645G>A		5_prime_UTR_variant	Exon 1 of 3		XP_011533312.1
FOXO1	XM_011535008.3	c.88-3392G>A		intron_variant	Intron 1 of 2		XP_011533310.1
FOXO1	XM_047430204.1	c.-81-3392G>A		intron_variant	Intron 1 of 2		XP_047286160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXO1	ENST00000379561.6	c.631-3392G>A		intron_variant	Intron 1 of 2	1	NM_002015.4	ENSP00000368880.4
ENSG00000288542	ENST00000636651.2	n.108-3392G>A		intron_variant	Intron 1 of 3	5
FOXO1	ENST00000655267.1	n.334-1490G>A		intron_variant	Intron 1 of 2
FOXO1	ENST00000660760.1	n.398-3392G>A		intron_variant	Intron 2 of 2

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

African (AFR) AF: 0.0745 AC: 3060 AN: 41070

American (AMR) AF: 0.0677 AC: 1027 AN: 15170

Ashkenazi Jewish (ASJ) AF: 0.0912 AC: 316 AN: 3466

East Asian (EAS) AF: 0.238 AC: 1226 AN: 5152

South Asian (SAS) AF: 0.109 AC: 506 AN: 4662

European-Finnish (FIN) AF: 0.0291 AC: 303 AN: 10404

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0649 AC: 4403 AN: 67844

Other (OTH) AF: 0.0891 AC: 187 AN: 2098

Alfa AF: 0.0636 Hom.: 51

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
PhyloP100		-0.33
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: rs2701858; hg19: chr13-41138389;