dbSNP rs886038680: FOXL2:p.Ser273Ser (chr3-138945904-C-G) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7

The NM_023067.4(FOXL2):c.819G>C(p.Ser273Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000303 in 1,319,250 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000017 ( 0 hom. )

Consequence

FOXL2
NM_023067.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0830

Publications

0 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: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 3-138945904-C-G is Benign according to our data. Variant chr3-138945904-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 261663.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.083 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXL2	NM_023067.4 link	c.819G>C	p.Ser273Ser	synonymous_variant	Exon 1 of 1	ENST00000648323.1	NP_075555.1	P58012Q53ZD3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXL2	ENST00000648323.1 link	c.819G>C	p.Ser273Ser	synonymous_variant	Exon 1 of 1		NM_023067.4	ENSP00000497217.1		P58012

Frequencies

GnomAD3 genomes

AF:

0.0000133

AC:

AN:

150678

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000660

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000171

AC:

AN:

1168572

Hom.:

Cov.:

AF XY:

0.00000356

AC XY:

AN XY:

562084

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24278

American (AMR)

AF:

0.00

AC:

AN:

14102

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15612

East Asian (EAS)

AF:

0.00

AC:

AN:

28614

South Asian (SAS)

AF:

0.00

AC:

AN:

33952

European-Finnish (FIN)

AF:

0.00

AC:

AN:

25694

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3310

European-Non Finnish (NFE)

AF:

0.00000205

AC:

AN:

975500

Other (OTH)

AF:

0.00

AC:

AN:

47510

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000133

AC:

AN:

150678

Hom.:

Cov.:

AF XY:

0.0000272

AC XY:

AN XY:

73554

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41162

American (AMR)

AF:

0.0000660

AC:

AN:

15150

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3452

East Asian (EAS)

AF:

0.00

AC:

AN:

5098

South Asian (SAS)

AF:

0.00

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10214

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

67498

Other (OTH)

AF:

0.00

AC:

AN:

2068

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

6.3

(source)

DANN

Benign

0.83

PhyloP100

0.083

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over