rs2951787

Positions:

• chr13-40587633-G-A

Variant summary

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

The NM_002015.4(FOXO1):​c.631-26773C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 152,064 control chromosomes in the GnomAD database, including 8,144 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 0.29 (8144 hom., cov: 32)
• Consequence: FOXO1 NM_002015.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.409

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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXO1	NM_002015.4	c.631-26773C>T		intron_variant		ENST00000379561.6
FOXO1	XM_011535010.3	c.-25026C>T		5_prime_UTR_variant	1/3
FOXO1	XM_011535008.3	c.87+26517C>T		intron_variant
FOXO1	XM_047430204.1	c.-81-26773C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXO1	ENST00000379561.6	c.631-26773C>T		intron_variant		1	NM_002015.4	P1
FOXO1	ENST00000655267.1	n.334-24871C>T		intron_variant, non_coding_transcript_variant
FOXO1	ENST00000660760.1	n.398-26773C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44201 AN: 151946 Hom.: 8151 Cov.: 32

Gnomad AFR AF: 0.0683

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.336

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

GnomAD4 genome AF: 0.291 AC: 44178 AN: 152064 Hom.: 8144 Cov.: 32 AF XY: 0.292 AC XY: 21728 AN XY: 74328

Gnomad4 AFR AF: 0.0681

Gnomad4 AMR AF: 0.382

Gnomad4 ASJ AF: 0.433

Gnomad4 EAS AF: 0.136

Gnomad4 SAS AF: 0.269

Gnomad4 FIN AF: 0.403

Gnomad4 NFE AF: 0.391

Gnomad4 OTH AF: 0.332

Alfa AF: 0.381 Hom.: 15783

Bravo AF: 0.282

Asia WGS AF: 0.159 AC: 556 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.56
DANN	Benign	0.40
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2951787; hg19: chr13-41161770; COSMIC: COSV65428355;