3-138944666-C-CA

Position:

• chr3-138944666-C-CA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_023067.4(FOXL2):​c.*925_*926insT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0552 in 233,188 control chromosomes in the GnomAD database, including 709 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.064 (591 hom., cov: 32)
  • Exomes 𝑓: 0.038 (118 hom.)
• Consequence: FOXL2 NM_023067.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.52

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 3-138944666-C-CA is Benign according to our data. Variant chr3-138944666-C-CA is described in ClinVar as [Benign]. Clinvar id is 1228805.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXL2	NM_023067.4	c.*925_*926insT		3_prime_UTR_variant	1/1	ENST00000648323.1	NP_075555.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXL2	ENST00000648323.1	c.*925_*926insT		3_prime_UTR_variant	1/1		NM_023067.4	ENSP00000497217	P1

Frequencies

GnomAD3 genomes AF: 0.0640 AC: 9744 AN: 152190 Hom.: 584 Cov.: 32

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0308

Gnomad ASJ AF: 0.0302

Gnomad EAS AF: 0.0323

Gnomad SAS AF: 0.0835

Gnomad FIN AF: 0.0628

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0208

Gnomad OTH AF: 0.0540

GnomAD4 exome AF: 0.0382 AC: 3086 AN: 80880 Hom.: 118 Cov.: 0 AF XY: 0.0374 AC XY: 1391 AN XY: 37172

Gnomad4 AFR exome AF: 0.151

Gnomad4 AMR exome AF: 0.0244

Gnomad4 ASJ exome AF: 0.0281

Gnomad4 EAS exome AF: 0.0915

Gnomad4 SAS exome AF: 0.0755

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0195

Gnomad4 OTH exome AF: 0.0304

GnomAD4 genome AF: 0.0642 AC: 9781 AN: 152308 Hom.: 591 Cov.: 32 AF XY: 0.0651 AC XY: 4847 AN XY: 74474

Gnomad4 AFR AF: 0.154

Gnomad4 AMR AF: 0.0308

Gnomad4 ASJ AF: 0.0302

Gnomad4 EAS AF: 0.0324

Gnomad4 SAS AF: 0.0836

Gnomad4 FIN AF: 0.0628

Gnomad4 NFE AF: 0.0208

Gnomad4 OTH AF: 0.0605

Alfa AF: 0.0494 Hom.: 37

Bravo AF: 0.0618

Asia WGS AF: 0.0720 AC: 252 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 22, 2019

This variant is associated with the following publications: (PMID: 15450400) -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs139209636; hg19: chr3-138663508;