rs2297627

Positions:

• chr13-40659794-A-G
• chr13-40659794-A-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+5789T>C 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 152,012 control chromosomes in the GnomAD database, including 14,245 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 (14245 hom., cov: 32)
• Consequence: FOXO1 NM_002015.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.696

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]

FOXO1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• 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	Protein	UniProt
FOXO1	NM_002015.4	c.630+5789T>C		intron_variant		ENST00000379561.6	NP_002006.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXO1	ENST00000379561.6	c.630+5789T>C		intron_variant		1	NM_002015.4	ENSP00000368880.4
FOXO1	ENST00000655267.1	n.333+5789T>C		intron_variant
FOXO1	ENST00000660760.1	n.295+5789T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62757 AN: 151892 Hom.: 14197 Cov.: 32

Gnomad AFR AF: 0.566

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.733

Gnomad SAS AF: 0.520

Gnomad FIN AF: 0.357

Gnomad MID AF: 0.299

Gnomad NFE AF: 0.306

Gnomad OTH AF: 0.399

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

GnomAD4 genome AF: 0.414 AC: 62869 AN: 152012 Hom.: 14245 Cov.: 32 AF XY: 0.419 AC XY: 31121 AN XY: 74300

Gnomad4 AFR AF: 0.567

Gnomad4 AMR AF: 0.414

Gnomad4 ASJ AF: 0.292

Gnomad4 EAS AF: 0.732

Gnomad4 SAS AF: 0.521

Gnomad4 FIN AF: 0.357

Gnomad4 NFE AF: 0.306

Gnomad4 OTH AF: 0.404

Alfa AF: 0.363 Hom.: 1770

Bravo AF: 0.423

Asia WGS AF: 0.645 AC: 2238 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.77
DANN	Benign	0.25

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: rs2297627; hg19: chr13-41233931;