chr13-40563667-A-C

Variant names:

• chr13-40563667-A-C
• rs2755209
• NM_002015.4:c.631-2807T>G

Variant summary

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

The NM_002015.4(FOXO1):​c.631-2807T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 151,794 control chromosomes in the GnomAD database, including 17,060 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 0.46 (17060 hom., cov: 30)
• Consequence: FOXO1 NM_002015.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.688
• Publications: 28 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002015.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXO1	NM_002015.4	MANE Select	c.631-2807T>G		intron	N/A	NP_002006.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXO1	ENST00000379561.6	TSL:1 MANE Select	c.631-2807T>G		intron	N/A	ENSP00000368880.4	Q12778
	FOXO1	ENST00000909775.1		c.631-2807T>G		intron	N/A	ENSP00000579834.1
	FOXO1	ENST00000962362.1		c.631-2807T>G		intron	N/A	ENSP00000632421.1

Frequencies

GnomAD3 genomes AF: 0.462 AC: 70039 AN: 151674 Hom.: 17020 Cov.: 30

Gnomad AFR AF: 0.567

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.482

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.756

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.481

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

GnomAD4 genome AF: 0.462 AC: 70143 AN: 151794 Hom.: 17060 Cov.: 30 AF XY: 0.465 AC XY: 34495 AN XY: 74172

African (AFR) AF: 0.567 AC: 23465 AN: 41358

American (AMR) AF: 0.483 AC: 7379 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.371 AC: 1286 AN: 3466

East Asian (EAS) AF: 0.755 AC: 3886 AN: 5146

South Asian (SAS) AF: 0.547 AC: 2621 AN: 4790

European-Finnish (FIN) AF: 0.392 AC: 4133 AN: 10548

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.379 AC: 25750 AN: 67908

Other (OTH) AF: 0.486 AC: 1022 AN: 2104

Alfa AF: 0.403 Hom.: 21700

Bravo AF: 0.473

Asia WGS AF: 0.673 AC: 2340 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.5
DANN	Benign	0.39
PhyloP100		-0.69
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2755209; hg19: chr13-41137804;