13-40569583-C-T

Variant names:

• chr13-40569583-C-T
• rs2721069
• NM_002015.4:c.631-8723G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002015.4(FOXO1):​c.631-8723G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 151,994 control chromosomes in the GnomAD database, including 13,389 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 0.40 (13389 hom., cov: 32)
• Consequence: FOXO1 NM_002015.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0390

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.712 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXO1	NM_002015.4	c.631-8723G>A		intron_variant	Intron 1 of 2	ENST00000379561.6	NP_002006.2
FOXO1	XM_011535010.3	c.-6976G>A		5_prime_UTR_variant	Exon 1 of 3		XP_011533312.1
FOXO1	XM_011535008.3	c.88-8723G>A		intron_variant	Intron 1 of 2		XP_011533310.1
FOXO1	XM_047430204.1	c.-81-8723G>A		intron_variant	Intron 1 of 2		XP_047286160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXO1	ENST00000379561.6	c.631-8723G>A		intron_variant	Intron 1 of 2	1	NM_002015.4	ENSP00000368880.4
ENSG00000288542	ENST00000636651.2	n.108-8723G>A		intron_variant	Intron 1 of 3	5
FOXO1	ENST00000655267.1	n.334-6821G>A		intron_variant	Intron 1 of 2
FOXO1	ENST00000660760.1	n.398-8723G>A		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61108 AN: 151876 Hom.: 13346 Cov.: 32

Gnomad AFR AF: 0.528

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.732

Gnomad SAS AF: 0.516

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.388

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

GnomAD4 genome AF: 0.403 AC: 61217 AN: 151994 Hom.: 13389 Cov.: 32 AF XY: 0.409 AC XY: 30374 AN XY: 74294

Gnomad4 AFR AF: 0.529

Gnomad4 AMR AF: 0.410

Gnomad4 ASJ AF: 0.296

Gnomad4 EAS AF: 0.731

Gnomad4 SAS AF: 0.516

Gnomad4 FIN AF: 0.359

Gnomad4 NFE AF: 0.305

Gnomad4 OTH AF: 0.394

Alfa AF: 0.359 Hom.: 1689

Bravo AF: 0.410

Asia WGS AF: 0.637 AC: 2212 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	4.8
DANN	Benign	0.63

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: rs2721069; hg19: chr13-41143720;