Genetic Variant FOXL2:c.*1451A>G (chr3-138944141-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_023067.4(FOXL2):c.*1451A>G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 197,238 control chromosomes in the GnomAD database, including 3,534 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 0.098 ( 2127 hom., cov: 33)

Exomes 𝑓: 0.12 ( 1407 hom. )

Consequence

FOXL2
NM_023067.4 downstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.797

Publications

3 publications found

Variant links:

Genes affected

FOXL2 (HGNC:1092): (forkhead box L2) This gene encodes a forkhead transcription factor. The protein contains a fork-head DNA-binding domain and may play a role in ovarian development and function. Expansion of a polyalanine repeat region and other mutations in this gene are a cause of blepharophimosis syndrome and premature ovarian failure 3. [provided by RefSeq, Jul 2016]

FOXL2 links:

LINC01391 (HGNC:50666): (long intergenic non-protein coding RNA 1391)

LINC01391 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.545 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXL2	NM_023067.4 link	c.*1451A>G		downstream_gene_variant		ENST00000648323.1	NP_075555.1
LINC01391	NR_121649.1 link	n.-121A>G		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXL2	ENST00000648323.1 link	c.*1451A>G		downstream_gene_variant			NM_023067.4	ENSP00000497217.1

Frequencies

GnomAD3 genomes

AF:

0.0983

AC:

14947

AN:

152132

Hom.:

2124

Cov.:

show subpopulations

Gnomad AFR

AF:

0.242

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.0471

Gnomad ASJ

AF:

0.0352

Gnomad EAS

AF:

0.564

Gnomad SAS

AF:

0.0548

Gnomad FIN

AF:

0.0274

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.00631

Gnomad OTH

AF:

0.0827

GnomAD4 exome

AF:

0.119

AC:

5366

AN:

44988

Hom.:

1407

Cov.:

AF XY:

0.116

AC XY:

2422

AN XY:

20950

show subpopulations

African (AFR)

AF:

0.219

AC:

391

AN:

1782

American (AMR)

AF:

0.0376

AC:

AN:

1170

Ashkenazi Jewish (ASJ)

AF:

0.0322

AC:

AN:

2890

East Asian (EAS)

AF:

0.603

AC:

4413

AN:

7318

South Asian (SAS)

AF:

0.0500

AC:

AN:

380

European-Finnish (FIN)

AF:

0.0238

AC:

AN:

Middle Eastern (MID)

AF:

0.0236

AC:

AN:

296

European-Non Finnish (NFE)

AF:

0.00620

AC:

169

AN:

27250

Other (OTH)

AF:

0.0597

AC:

228

AN:

3818

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

124

249

373

498

622

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

176

220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0984

AC:

14986

AN:

152250

Hom.:

2127

Cov.:

AF XY:

0.100

AC XY:

7454

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.242

AC:

10038

AN:

41518

American (AMR)

AF:

0.0473

AC:

724

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0352

AC:

122

AN:

3470

East Asian (EAS)

AF:

0.562

AC:

2909

AN:

5172

South Asian (SAS)

AF:

0.0538

AC:

260

AN:

4834

European-Finnish (FIN)

AF:

0.0274

AC:

291

AN:

10610

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00631

AC:

429

AN:

68030

Other (OTH)

AF:

0.0885

AC:

187

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

546

1091

1637

2182

2728

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

288

432

576

720

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0460

Hom.:

260

Bravo

AF:

0.108

Asia WGS

AF:

0.287

AC:

999

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

(source)

DANN

Benign

0.68

PhyloP100

0.80

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over