NM_002015.4:c.631-51504C>T

Variant names:

• chr13-40612364-G-A
• rs10507486
• NM_002015.4:c.631-51504C>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.631-51504C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 152,164 control chromosomes in the GnomAD database, including 2,546 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 0.17 (2546 hom., cov: 32)
• Consequence: FOXO1 NM_002015.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.150
• Publications: 22 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.28 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.631-51504C>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.631-51504C>T		intron	N/A	ENSP00000368880.4
	FOXO1	ENST00000655267.1		n.334-49602C>T		intron	N/A
	FOXO1	ENST00000660760.1		n.397+20783C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25821 AN: 152044 Hom.: 2545 Cov.: 32

Gnomad AFR AF: 0.0791

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.0918

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.155

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

GnomAD4 genome AF: 0.170 AC: 25826 AN: 152164 Hom.: 2546 Cov.: 32 AF XY: 0.174 AC XY: 12967 AN XY: 74380

African (AFR) AF: 0.0790 AC: 3279 AN: 41520

American (AMR) AF: 0.204 AC: 3119 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 556 AN: 3466

East Asian (EAS) AF: 0.0916 AC: 475 AN: 5186

South Asian (SAS) AF: 0.292 AC: 1405 AN: 4806

European-Finnish (FIN) AF: 0.235 AC: 2485 AN: 10578

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.207 AC: 14050 AN: 67994

Other (OTH) AF: 0.153 AC: 322 AN: 2104

Alfa AF: 0.189 Hom.: 511

Bravo AF: 0.160

Asia WGS AF: 0.183 AC: 636 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.8
DANN	Benign	0.36
PhyloP100		-0.15
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: rs10507486; hg19: chr13-41186501;