chr13-40607637-T-A

Variant names:

• chr13-40607637-T-A
• rs3908773
• NM_002015.4:c.631-46777A>T

Variant summary

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

The NM_002015.4(FOXO1):​c.631-46777A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 152,186 control chromosomes in the GnomAD database, including 4,542 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 0.20 (4542 hom., cov: 33)
• Consequence: FOXO1 NM_002015.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.760
• Publications: 5 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.622 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.631-46777A>T		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.631-46777A>T		intron	N/A	ENSP00000368880.4
	ENSG00000288542	ENST00000636651.2	TSL:5	n.107+3384A>T		intron	N/A
	FOXO1	ENST00000655267.1		n.334-44875A>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30293 AN: 152068 Hom.: 4518 Cov.: 33

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.641

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.0929

Gnomad OTH AF: 0.204

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

GnomAD4 genome AF: 0.200 AC: 30368 AN: 152186 Hom.: 4542 Cov.: 33 AF XY: 0.202 AC XY: 15000 AN XY: 74432

African (AFR) AF: 0.353 AC: 14619 AN: 41468

American (AMR) AF: 0.183 AC: 2802 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 423 AN: 3470

East Asian (EAS) AF: 0.640 AC: 3313 AN: 5174

South Asian (SAS) AF: 0.198 AC: 957 AN: 4832

European-Finnish (FIN) AF: 0.122 AC: 1298 AN: 10610

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.0929 AC: 6318 AN: 68014

Other (OTH) AF: 0.212 AC: 448 AN: 2116

Alfa AF: 0.0399 Hom.: 22

Bravo AF: 0.213

Asia WGS AF: 0.436 AC: 1513 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.19
DANN	Benign	0.59
PhyloP100		-0.76
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: rs3908773; hg19: chr13-41181774;