rs1923249

Positions:

• chr13-40569744-C-A
• chr13-40569744-C-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.89).
• 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/exons	MANE	Protein	UniProt
FOXO1	NM_002015.4	c.631-8884G>T		intron_variant		ENST00000379561.6	NP_002006.2
FOXO1	XM_011535010.3	c.-7137G>T		5_prime_UTR_variant	1/3		XP_011533312.1
FOXO1	XM_011535008.3	c.88-8884G>T		intron_variant			XP_011533310.1
FOXO1	XM_047430204.1	c.-81-8884G>T		intron_variant			XP_047286160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXO1	ENST00000379561.6	c.631-8884G>T		intron_variant		1	NM_002015.4	ENSP00000368880	P1
FOXO1	ENST00000655267.1	n.334-6982G>T		intron_variant, non_coding_transcript_variant
FOXO1	ENST00000660760.1	n.398-8884G>T		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.524

Gnomad4 AMR AF: 0.410

Gnomad4 ASJ AF: 0.296

Gnomad4 EAS AF: 0.732

Gnomad4 SAS AF: 0.517

Gnomad4 FIN AF: 0.359

Gnomad4 NFE AF: 0.305

Gnomad4 OTH AF: 0.395

Alfa AF: 0.307 Hom.: 2816

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

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: rs1923249; hg19: chr13-41143881;