rs144907712

Variant names:

• chr13-40560005-C-T
• rs144907712
• NM_002015.4:c.1486G>A

Your query was ambiguous. Multiple possible variants found:

• chr13-40560005-C-T
• chr13-40560005-C-A
• chr13-40560005-C-G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_002015.4(FOXO1):​c.1486G>A​(p.Val496Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000018 in 1,614,022 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: FOXO1 NM_002015.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.73
• Publications: 0 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.18555829).
• BS2: High AC in GnomAd4 at 16 AD gene.

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.1486G>A	p.Val496Ile	missense	Exon 2 of 3	NP_002006.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXO1	ENST00000379561.6	TSL:1 MANE Select	c.1486G>A	p.Val496Ile	missense	Exon 2 of 3	ENSP00000368880.4	Q12778
	FOXO1	ENST00000909775.1		c.1486G>A	p.Val496Ile	missense	Exon 2 of 2	ENSP00000579834.1
	FOXO1	ENST00000962362.1		c.1486G>A	p.Val496Ile	missense	Exon 2 of 3	ENSP00000632421.1

Frequencies

GnomAD3 genomes AF: 0.000105 AC: 16 AN: 152164 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000362

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000279 AC: 7 AN: 251272 AF XY: 0.0000221

Gnomad AFR exome AF: 0.000369

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000463

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000889 AC: 13 AN: 1461858 Hom.: 0 Cov.: 32 AF XY: 0.00000963 AC XY: 7 AN XY: 727234

African (AFR) AF: 0.000239 AC: 8 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.0000375 AC: 2 AN: 53388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1112008

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome AF: 0.000105 AC: 16 AN: 152164 Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11 AN XY: 74356

African (AFR) AF: 0.000362 AC: 15 AN: 41446

American (AMR) AF: 0.0000654 AC: 1 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.000197 Hom.: 0

Bravo AF: 0.000125

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.11
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.35	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.19	T
MetaSVM	Uncertain	0.28	D
MutationAssessor	Benign	1.9	M
PhyloP100		4.7
PrimateAI	Benign	0.38	T
PROVEAN	Benign	0.050	N
REVEL	Benign	0.27
Sift	Benign	0.40	T
Sift4G	Benign	0.75	T
Polyphen		0.90	P
Vest4		0.34
MVP		0.81
MPC		0.38
ClinPred		0.23	T
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.054
gMVP		0.13
Mutation Taster		=96/4	polymorphism

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: rs144907712; hg19: chr13-41134142; COSMIC: COSV65427504;