13-40629768-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.713 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXO1	NM_002015.4	c.630+35815G>A		intron_variant		ENST00000379561.6
FOXO1	XM_047430204.1	c.-82+15571G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXO1	ENST00000379561.6	c.630+35815G>A		intron_variant		1	NM_002015.4	P1
FOXO1	ENST00000655267.1	n.333+35815G>A		intron_variant, non_coding_transcript_variant
FOXO1	ENST00000660760.1	n.397+3379G>A		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.567

Gnomad4 AMR AF: 0.414

Gnomad4 ASJ AF: 0.293

Gnomad4 EAS AF: 0.733

Gnomad4 SAS AF: 0.520

Gnomad4 FIN AF: 0.358

Gnomad4 NFE AF: 0.306

Gnomad4 OTH AF: 0.406

Alfa AF: 0.365 Hom.: 1365

Bravo AF: 0.423

Asia WGS AF: 0.645 AC: 2240 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	3.0
Dann	Benign	0.60

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: rs4581585; hg19: chr13-41203905;