Variant 16-86579393-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_005250.3(FOXL1):c.670G>A(p.Gly224Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00165 in 1,523,378 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0017 ( 4 hom. )

Consequence

FOXL1
NM_005250.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.400

Variant links:

Genes affected

FOXL1 (HGNC:3817): (forkhead box L1) This gene encodes a member of the forkhead/winged helix-box (FOX) family of transcription factors. FOX transcription factors are characterized by a distinct DNA-binding forkhead domain and play critical roles in the regulation of multiple processes including metabolism, cell proliferation and gene expression during ontogenesis. [provided by RefSeq, Nov 2012]

FOXL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.035634458).

BS2

High AC in GnomAd at 188 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXL1	NM_005250.3 linkuse as main transcript	c.670G>A	p.Gly224Ser	missense_variant	1/1	ENST00000320241.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXL1	ENST00000320241.5 linkuse as main transcript	c.670G>A	p.Gly224Ser	missense_variant	1/1		NM_005250.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00124

AC:

188

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00141

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00229

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00104

AC:

124

AN:

119230

Hom.:

AF XY:

0.00103

AC XY:

AN XY:

65278

show subpopulations

Gnomad AFR exome

AF:

0.000343

Gnomad AMR exome

AF:

0.0000475

Gnomad ASJ exome

AF:

0.000153

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00179

Gnomad NFE exome

AF:

0.00231

Gnomad OTH exome

AF:

0.000561

GnomAD4 exome

AF:

0.00170

AC:

2332

AN:

1371172

Hom.:

Cov.:

AF XY:

0.00167

AC XY:

1129

AN XY:

675776

show subpopulations

Gnomad4 AFR exome

AF:

0.000261

Gnomad4 AMR exome

AF:

0.000125

Gnomad4 ASJ exome

AF:

0.0000421

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00164

Gnomad4 NFE exome

AF:

0.00205

Gnomad4 OTH exome

AF:

0.000914

GnomAD4 genome

AF:

0.00124

AC:

188

AN:

152206

Hom.:

Cov.:

AF XY:

0.00118

AC XY:

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00141

Gnomad4 NFE

AF:

0.00230

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00160

Hom.:

Bravo

AF:

0.00108

ExAC

AF:

0.000278

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 27, 2023

The c.670G>A (p.G224S) alteration is located in exon 1 (coding exon 1) of the FOXL1 gene. This alteration results from a G to A substitution at nucleotide position 670, causing the glycine (G) at amino acid position 224 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.31

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.093

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.44

M_CAP

Pathogenic

0.96

MetaRNN

Benign

0.036

MetaSVM

Benign

-0.44

MutationAssessor

Benign

0.97

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.75

PROVEAN

Benign

0.40

REVEL

Benign

0.24

Sift

Benign

0.24

Sift4G

Benign

0.32

Polyphen

0.010

Vest4

0.098

MVP

0.73

ClinPred

0.0065

GERP RS

1.7

Varity_R

0.036

gMVP

0.28

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over