13-40629878-T-C

Variant names:

• chr13-40629878-T-C
• rs7323267
• NM_002015.4:c.630+35705A>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.630+35705A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 152,068 control chromosomes in the GnomAD database, including 2,253 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 (2253 hom., cov: 32)
• Consequence: FOXO1 NM_002015.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.255 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.630+35705A>G		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.630+35705A>G		intron	N/A	ENSP00000368880.4
	FOXO1	ENST00000655267.1		n.333+35705A>G		intron	N/A
	FOXO1	ENST00000660760.1		n.397+3269A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22898 AN: 151950 Hom.: 2254 Cov.: 32

Gnomad AFR AF: 0.0365

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.0413

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.141

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

GnomAD4 genome AF: 0.151 AC: 22897 AN: 152068 Hom.: 2253 Cov.: 32 AF XY: 0.154 AC XY: 11479 AN XY: 74310

African (AFR) AF: 0.0364 AC: 1513 AN: 41532

American (AMR) AF: 0.192 AC: 2931 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 523 AN: 3470

East Asian (EAS) AF: 0.0410 AC: 212 AN: 5172

South Asian (SAS) AF: 0.267 AC: 1282 AN: 4794

European-Finnish (FIN) AF: 0.219 AC: 2304 AN: 10544

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13713 AN: 67956

Other (OTH) AF: 0.139 AC: 293 AN: 2112

Alfa AF: 0.176 Hom.: 482

Bravo AF: 0.140

Asia WGS AF: 0.142 AC: 493 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.9
DANN	Benign	0.71
PhyloP100		-1.3
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: rs7323267; hg19: chr13-41204015;