rs3908773

Positions:

• chr13-40607637-T-A
• chr13-40607637-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXO1	NM_002015.4	c.631-46777A>T		intron_variant		ENST00000379561.6
FOXO1	XM_011535008.3	c.87+6513A>T		intron_variant
FOXO1	XM_047430204.1	c.-82+37702A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXO1	ENST00000379561.6	c.631-46777A>T		intron_variant		1	NM_002015.4	P1
FOXO1	ENST00000655267.1	n.334-44875A>T		intron_variant, non_coding_transcript_variant
FOXO1	ENST00000660760.1	n.397+25510A>T		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.353

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.122

Gnomad4 EAS AF: 0.640

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.0929

Gnomad4 OTH AF: 0.212

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.19
DANN	Benign	0.59

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

Publications

LitVar

Other links and lift over

dbSNP: rs3908773; hg19: chr13-41181774;