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

Variant summary

Our verdict is Benign. Variant got -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

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 made for transcript

Verdict is Benign. Variant got -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	P58012Q53ZD3
LINC01391	NR_121649.1 link	n.-121A>G		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
FOXL2	ENST00000648323.1 link	c.*1451A>G	downstream_gene_variant		NM_023067.4	ENSP00000497217.1	P58012
LINC01391	ENST00000483650.1 link	n.-138A>G	upstream_gene_variant	3
LINC01391	ENST00000495287.1 link	n.-121A>G	upstream_gene_variant	2

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

Gnomad4 AFR exome

AF:

0.219

Gnomad4 AMR exome

AF:

0.0376

Gnomad4 ASJ exome

AF:

0.0322

Gnomad4 EAS exome

AF:

0.603

Gnomad4 SAS exome

AF:

0.0500

Gnomad4 FIN exome

AF:

0.0238

Gnomad4 NFE exome

AF:

0.00620

Gnomad4 OTH exome

AF:

0.0597

GnomAD4 genome

AF:

0.0984

AC:

14986

AN:

152250

Hom.:

2127

Cov.:

AF XY:

0.100

AC XY:

7454

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.242

Gnomad4 AMR

AF:

0.0473

Gnomad4 ASJ

AF:

0.0352

Gnomad4 EAS

AF:

0.562

Gnomad4 SAS

AF:

0.0538

Gnomad4 FIN

AF:

0.0274

Gnomad4 NFE

AF:

0.00631

Gnomad4 OTH

AF:

0.0885

Alfa

AF:

0.0466

Hom.:

229

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

DANN

Benign

0.68

Splicing

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over