chr13-40587633-G-A

Variant names:

• chr13-40587633-G-A
• rs2951787
• NM_002015.4:c.631-26773C>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.631-26773C>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
• Publications: 12 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002015.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXO1	NM_002015.4	MANE Select	c.631-26773C>T		intron	N/A	NP_002006.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXO1	ENST00000379561.6	TSL:1 MANE Select	c.631-26773C>T		intron	N/A	ENSP00000368880.4
	ENSG00000288542	ENST00000636651.2	TSL:5	n.107+23388C>T		intron	N/A
	FOXO1	ENST00000655267.1		n.334-24871C>T		intron	N/A

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

African (AFR) AF: 0.0681 AC: 2828 AN: 41506

American (AMR) AF: 0.382 AC: 5841 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.433 AC: 1505 AN: 3472

East Asian (EAS) AF: 0.136 AC: 705 AN: 5172

South Asian (SAS) AF: 0.269 AC: 1294 AN: 4816

European-Finnish (FIN) AF: 0.403 AC: 4249 AN: 10556

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.391 AC: 26568 AN: 67950

Other (OTH) AF: 0.332 AC: 700 AN: 2106

Alfa AF: 0.367 Hom.: 20697

Bravo AF: 0.282

Asia WGS AF: 0.159 AC: 556 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.56
DANN	Benign	0.40
PhyloP100		-0.41
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2951787; hg19: chr13-41161770; COSMIC: COSV65428355;