dbSNP rs11924939: FOXL2:c.-232G>A (chr3-138946954-C-T) – 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.-232G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 610,648 control chromosomes in the GnomAD database, including 11,713 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 0.15 ( 2347 hom., cov: 33)

Exomes 𝑓: 0.19 ( 9366 hom. )

Consequence

FOXL2
NM_023067.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.402

Publications

12 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 Gene-Disease associations (from GenCC):

blepharophimosis, ptosis, and epicanthus inversus syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
premature ovarian failure 3
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

FOXL2 links:

Genome browser will be placed here

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=-0.5).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXL2	NM_023067.4 link	c.-232G>A		5_prime_UTR_variant	Exon 1 of 1	ENST00000648323.1	NP_075555.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXL2	ENST00000648323.1 link	c.-232G>A		5_prime_UTR_variant	Exon 1 of 1		NM_023067.4	ENSP00000497217.1

Frequencies

GnomAD3 genomes

AF:

0.152

AC:

23083

AN:

152106

Hom.:

2347

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0443

Gnomad AMI

AF:

0.310

Gnomad AMR

AF:

0.145

Gnomad ASJ

AF:

0.249

Gnomad EAS

AF:

0.00155

Gnomad SAS

AF:

0.0530

Gnomad FIN

AF:

0.181

Gnomad MID

AF:

0.253

Gnomad NFE

AF:

0.225

Gnomad OTH

AF:

0.172

GnomAD4 exome

AF:

0.185

AC:

85027

AN:

458424

Hom.:

9366

Cov.:

AF XY:

0.182

AC XY:

43272

AN XY:

237936

show subpopulations

African (AFR)

AF:

0.0454

AC:

437

AN:

9620

American (AMR)

AF:

0.131

AC:

1908

AN:

14522

Ashkenazi Jewish (ASJ)

AF:

0.244

AC:

3113

AN:

12770

East Asian (EAS)

AF:

0.000334

AC:

AN:

26974

South Asian (SAS)

AF:

0.0631

AC:

2398

AN:

37980

European-Finnish (FIN)

AF:

0.181

AC:

7377

AN:

40842

Middle Eastern (MID)

AF:

0.176

AC:

340

AN:

1928

European-Non Finnish (NFE)

AF:

0.225

AC:

64771

AN:

288270

Other (OTH)

AF:

0.183

AC:

4674

AN:

25518

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

3453

6906

10359

13812

17265

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

564

1128

1692

2256

2820

<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:

0.152

AC:

23075

AN:

152224

Hom.:

2347

Cov.:

AF XY:

0.147

AC XY:

10964

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.0442

AC:

1837

AN:

41568

American (AMR)

AF:

0.145

AC:

2217

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.249

AC:

864

AN:

3472

East Asian (EAS)

AF:

0.00155

AC:

AN:

5162

South Asian (SAS)

AF:

0.0528

AC:

255

AN:

4826

European-Finnish (FIN)

AF:

0.181

AC:

1916

AN:

10602

Middle Eastern (MID)

AF:

0.252

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.225

AC:

15262

AN:

67974

Other (OTH)

AF:

0.170

AC:

360

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

961

1922

2884

3845

4806

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

238

476

714

952

1190

<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:

0.183

Hom.:

663

Bravo

AF:

0.148

Asia WGS

AF:

0.0270

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Benign

0.95

PhyloP100

0.40

PromoterAI

-0.049

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

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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