13-40572164-T-C

Variant names:

• chr13-40572164-T-C
• rs2755213
• NM_002015.4:c.631-11304A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002015.4(FOXO1):​c.631-11304A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 152,160 control chromosomes in the GnomAD database, including 2,514 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 0.15 (2514 hom., cov: 32)
• Consequence: FOXO1 NM_002015.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23
• 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]

ENSG00000288542 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.622 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXO1	NM_002015.4	MANE Select	c.631-11304A>G		intron	N/A	NP_002006.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXO1	ENST00000379561.6	TSL:1 MANE Select	c.631-11304A>G		intron	N/A	ENSP00000368880.4	Q12778
	FOXO1	ENST00000909775.1		c.631-11304A>G		intron	N/A	ENSP00000579834.1
	FOXO1	ENST00000962362.1		c.631-11304A>G		intron	N/A	ENSP00000632421.1

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22532 AN: 152042 Hom.: 2497 Cov.: 32

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.194

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.641

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0920

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.148 AC: 22581 AN: 152160 Hom.: 2514 Cov.: 32 AF XY: 0.153 AC XY: 11367 AN XY: 74386

African (AFR) AF: 0.174 AC: 7212 AN: 41494

American (AMR) AF: 0.167 AC: 2550 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 422 AN: 3470

East Asian (EAS) AF: 0.641 AC: 3312 AN: 5170

South Asian (SAS) AF: 0.197 AC: 950 AN: 4814

European-Finnish (FIN) AF: 0.122 AC: 1297 AN: 10604

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.0920 AC: 6254 AN: 68008

Other (OTH) AF: 0.175 AC: 368 AN: 2106

Alfa AF: 0.115 Hom.: 4230

Bravo AF: 0.156

Asia WGS AF: 0.423 AC: 1471 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.030
DANN	Benign	0.63
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: rs2755213; hg19: chr13-41146301;