13-40629768-C-T

Variant names:

• chr13-40629768-C-T
• rs4581585
• NM_002015.4:c.630+35815G>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.630+35815G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 151,976 control chromosomes in the GnomAD database, including 14,250 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 0.41 (14250 hom., cov: 32)
• Consequence: FOXO1 NM_002015.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.120
• Publications: 8 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• 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.630+35815G>A		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.630+35815G>A		intron	N/A	ENSP00000368880.4	Q12778
	FOXO1	ENST00000909775.1		c.630+35815G>A		intron	N/A	ENSP00000579834.1
	FOXO1	ENST00000962362.1		c.630+35815G>A		intron	N/A	ENSP00000632421.1

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62768 AN: 151858 Hom.: 14201 Cov.: 32

Gnomad AFR AF: 0.566

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.734

Gnomad SAS AF: 0.519

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.306

Gnomad OTH AF: 0.401

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

GnomAD4 genome AF: 0.414 AC: 62881 AN: 151976 Hom.: 14250 Cov.: 32 AF XY: 0.419 AC XY: 31127 AN XY: 74262

African (AFR) AF: 0.567 AC: 23481 AN: 41424

American (AMR) AF: 0.414 AC: 6322 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1014 AN: 3464

East Asian (EAS) AF: 0.733 AC: 3789 AN: 5170

South Asian (SAS) AF: 0.520 AC: 2501 AN: 4814

European-Finnish (FIN) AF: 0.358 AC: 3779 AN: 10542

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.306 AC: 20794 AN: 67966

Other (OTH) AF: 0.406 AC: 858 AN: 2114

Alfa AF: 0.373 Hom.: 1486

Bravo AF: 0.423

Asia WGS AF: 0.645 AC: 2240 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.0
DANN	Benign	0.60
PhyloP100		0.12
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4581585;

hg19: chr13-41203905;