13-40599271-G-C

Variant names:

• chr13-40599271-G-C
• rs4943794
• NM_002015.4:c.631-38411C>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.631-38411C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 150,744 control chromosomes in the GnomAD database, including 2,510 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 0.17 (2510 hom., cov: 31)
• Consequence: FOXO1 NM_002015.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.747
• Publications: 22 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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.285 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXO1	NM_002015.4	MANE Select	c.631-38411C>G		intron	N/A	NP_002006.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXO1	ENST00000379561.6	TSL:1 MANE Select	c.631-38411C>G		intron	N/A	ENSP00000368880.4
	ENSG00000288542	ENST00000636651.2	TSL:5	n.107+11750C>G		intron	N/A
	FOXO1	ENST00000655267.1		n.334-36509C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25688 AN: 150682 Hom.: 2508 Cov.: 31

Gnomad AFR AF: 0.0791

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.0925

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.109

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.158

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

GnomAD4 genome AF: 0.170 AC: 25692 AN: 150744 Hom.: 2510 Cov.: 31 AF XY: 0.175 AC XY: 12902 AN XY: 73528

African (AFR) AF: 0.0791 AC: 3245 AN: 41046

American (AMR) AF: 0.203 AC: 3092 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 556 AN: 3458

East Asian (EAS) AF: 0.0923 AC: 472 AN: 5112

South Asian (SAS) AF: 0.298 AC: 1424 AN: 4778

European-Finnish (FIN) AF: 0.241 AC: 2438 AN: 10124

Middle Eastern (MID) AF: 0.110 AC: 32 AN: 290

European-Non Finnish (NFE) AF: 0.207 AC: 14004 AN: 67726

Other (OTH) AF: 0.156 AC: 327 AN: 2090

Alfa AF: 0.193 Hom.: 421

Bravo AF: 0.160

Asia WGS AF: 0.184 AC: 639 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.54
DANN	Benign	0.33
PhyloP100		-0.75
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: rs4943794; hg19: chr13-41173408;