13-40565575-T-C

Variant names:

• chr13-40565575-T-C
• rs2721068
• NM_002015.4:c.631-4715A>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.631-4715A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 152,036 control chromosomes in the GnomAD database, including 12,690 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 0.38 (12690 hom., cov: 32)
• Consequence: FOXO1 NM_002015.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0330
• Publications: 19 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.713 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.631-4715A>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.631-4715A>G		intron	N/A	ENSP00000368880.4	Q12778
	FOXO1	ENST00000909775.1		c.631-4715A>G		intron	N/A	ENSP00000579834.1
	FOXO1	ENST00000962362.1		c.631-4715A>G		intron	N/A	ENSP00000632421.1

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57673 AN: 151918 Hom.: 12645 Cov.: 32

Gnomad AFR AF: 0.559

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.733

Gnomad SAS AF: 0.503

Gnomad FIN AF: 0.280

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.373

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

GnomAD4 genome AF: 0.380 AC: 57782 AN: 152036 Hom.: 12690 Cov.: 32 AF XY: 0.386 AC XY: 28656 AN XY: 74308

African (AFR) AF: 0.559 AC: 23172 AN: 41458

American (AMR) AF: 0.396 AC: 6059 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 932 AN: 3468

East Asian (EAS) AF: 0.732 AC: 3778 AN: 5160

South Asian (SAS) AF: 0.504 AC: 2421 AN: 4808

European-Finnish (FIN) AF: 0.280 AC: 2958 AN: 10572

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.255 AC: 17300 AN: 67968

Other (OTH) AF: 0.379 AC: 801 AN: 2116

Alfa AF: 0.317 Hom.: 1091

Bravo AF: 0.395

Asia WGS AF: 0.629 AC: 2184 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.50
PhyloP100		-0.033
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: rs2721068; hg19: chr13-41139712;