chr13-40628247-G-A

Variant names:

• chr13-40628247-G-A
• rs12854161
• NM_002015.4:c.630+37336C>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.630+37336C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 151,644 control chromosomes in the GnomAD database, including 3,261 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 0.20 (3261 hom., cov: 30)
• Consequence: FOXO1 NM_002015.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.223
• Publications: 11 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=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.258 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+37336C>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.630+37336C>T		intron	N/A	ENSP00000368880.4
	FOXO1	ENST00000655267.1		n.333+37336C>T		intron	N/A
	FOXO1	ENST00000660760.1		n.397+4900C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29881 AN: 151524 Hom.: 3259 Cov.: 30

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.204

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.187

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

GnomAD4 genome AF: 0.197 AC: 29881 AN: 151644 Hom.: 3261 Cov.: 30 AF XY: 0.193 AC XY: 14292 AN XY: 74066

African (AFR) AF: 0.115 AC: 4733 AN: 41326

American (AMR) AF: 0.153 AC: 2332 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 613 AN: 3470

East Asian (EAS) AF: 0.109 AC: 564 AN: 5158

South Asian (SAS) AF: 0.183 AC: 881 AN: 4806

European-Finnish (FIN) AF: 0.222 AC: 2321 AN: 10458

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.262 AC: 17757 AN: 67880

Other (OTH) AF: 0.187 AC: 393 AN: 2106

Alfa AF: 0.228 Hom.: 12076

Bravo AF: 0.187

Asia WGS AF: 0.155 AC: 538 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.5
DANN	Benign	0.79
PhyloP100		-0.22
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: rs12854161; hg19: chr13-41202384;