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GeneBe

13-40560570-A-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_002015.4(FOXO1):c.921T>C(p.Phe307=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00157 in 1,614,222 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 2 hom., cov: 32)
Exomes 𝑓: 0.0016 ( 1 hom. )

Consequence

FOXO1
NM_002015.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.289
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.58).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 13-40560570-A-G is Benign according to our data. Variant chr13-40560570-A-G is described in ClinVar as [Benign]. Clinvar id is 708958.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.289 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 209 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FOXO1NM_002015.4 linkuse as main transcriptc.921T>C p.Phe307= synonymous_variant 2/3 ENST00000379561.6
FOXO1XM_011535008.3 linkuse as main transcriptc.378T>C p.Phe126= synonymous_variant 2/3
FOXO1XM_011535010.3 linkuse as main transcriptc.210T>C p.Phe70= synonymous_variant 2/3
FOXO1XM_047430204.1 linkuse as main transcriptc.210T>C p.Phe70= synonymous_variant 2/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FOXO1ENST00000379561.6 linkuse as main transcriptc.921T>C p.Phe307= synonymous_variant 2/31 NM_002015.4 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00137
AC:
209
AN:
152214
Hom.:
2
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000289
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00471
Gnomad ASJ
AF:
0.00288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000471
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00156
Gnomad OTH
AF:
0.00192
GnomAD3 exomes
AF:
0.00145
AC:
364
AN:
251230
Hom.:
0
AF XY:
0.00150
AC XY:
203
AN XY:
135776
show subpopulations
Gnomad AFR exome
AF:
0.000431
Gnomad AMR exome
AF:
0.00312
Gnomad ASJ exome
AF:
0.00248
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000523
Gnomad FIN exome
AF:
0.000323
Gnomad NFE exome
AF:
0.00165
Gnomad OTH exome
AF:
0.00228
GnomAD4 exome
AF:
0.00159
AC:
2323
AN:
1461890
Hom.:
1
Cov.:
32
AF XY:
0.00158
AC XY:
1151
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.000358
Gnomad4 AMR exome
AF:
0.00302
Gnomad4 ASJ exome
AF:
0.00241
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000487
Gnomad4 FIN exome
AF:
0.000243
Gnomad4 NFE exome
AF:
0.00174
Gnomad4 OTH exome
AF:
0.00177
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00137
AC:
209
AN:
152332
Hom.:
2
Cov.:
32
AF XY:
0.00141
AC XY:
105
AN XY:
74484
show subpopulations
Gnomad4 AFR
AF:
0.000289
Gnomad4 AMR
AF:
0.00470
Gnomad4 ASJ
AF:
0.00288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000471
Gnomad4 NFE
AF:
0.00156
Gnomad4 OTH
AF:
0.00190
Alfa
AF:
0.00163
Hom.:
0
Bravo
AF:
0.00168
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.00202
EpiControl
AF:
0.00207

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.58
Cadd
Benign
5.7
Dann
Benign
0.53

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs45624735; hg19: chr13-41134707; COSMIC: COSV101092183; COSMIC: COSV101092183; API