13-40569744-C-A

Variant names:

• chr13-40569744-C-A
• rs1923249
• NM_002015.4:c.631-8884G>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.631-8884G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 151,984 control chromosomes in the GnomAD database, including 13,290 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 (13290 hom., cov: 32)
• Consequence: FOXO1 NM_002015.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20
• 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=-0.89).
• 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 rank	MANE	Protein	UniProt
FOXO1	NM_002015.4	c.631-8884G>T		intron_variant	Intron 1 of 2	ENST00000379561.6	NP_002006.2
FOXO1	XM_011535010.3	c.-7137G>T		5_prime_UTR_variant	Exon 1 of 3		XP_011533312.1
FOXO1	XM_011535008.3	c.88-8884G>T		intron_variant	Intron 1 of 2		XP_011533310.1
FOXO1	XM_047430204.1	c.-81-8884G>T		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.631-8884G>T		intron_variant	Intron 1 of 2	1	NM_002015.4	ENSP00000368880.4
ENSG00000288542	ENST00000636651.2	n.108-8884G>T		intron_variant	Intron 1 of 3	5
FOXO1	ENST00000655267.1	n.334-6982G>T		intron_variant	Intron 1 of 2
FOXO1	ENST00000660760.1	n.398-8884G>T		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60920 AN: 151864 Hom.: 13247 Cov.: 32

Gnomad AFR AF: 0.524

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.733

Gnomad SAS AF: 0.516

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.296

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.389

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

GnomAD4 genome AF: 0.402 AC: 61023 AN: 151984 Hom.: 13290 Cov.: 32 AF XY: 0.408 AC XY: 30261 AN XY: 74242

African (AFR) AF: 0.524 AC: 21725 AN: 41446

American (AMR) AF: 0.410 AC: 6259 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 1028 AN: 3472

East Asian (EAS) AF: 0.732 AC: 3763 AN: 5138

South Asian (SAS) AF: 0.517 AC: 2489 AN: 4818

European-Finnish (FIN) AF: 0.359 AC: 3787 AN: 10550

Middle Eastern (MID) AF: 0.298 AC: 87 AN: 292

European-Non Finnish (NFE) AF: 0.305 AC: 20763 AN: 67964

Other (OTH) AF: 0.395 AC: 834 AN: 2112

Alfa AF: 0.319 Hom.: 3700

Bravo AF: 0.408

Asia WGS AF: 0.633 AC: 2198 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.17
DANN	Benign	0.59
PhyloP100		-1.2
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: rs1923249; hg19: chr13-41143881;