3-138944973-G-T

Position:

• chr3-138944973-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_023067.4(FOXL2):​c.*619C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00366 in 232,940 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0034 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0041 (1 hom.)
• Consequence: FOXL2 NM_023067.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.364

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 3-138944973-G-T is Benign according to our data. Variant chr3-138944973-G-T is described in ClinVar as [Benign]. Clinvar id is 1685141.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00342 (521/152344) while in subpopulation SAS AF= 0.00704 (34/4832). AF 95% confidence interval is 0.00518. There are 0 homozygotes in gnomad4. There are 248 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 521 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXL2	NM_023067.4	c.*619C>A		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	c.*619C>A		3_prime_UTR_variant	1/1		NM_023067.4	ENSP00000497217.1

Frequencies

GnomAD3 genomes AF: 0.00344 AC: 523 AN: 152226 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000916

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00347

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00724

Gnomad FIN AF: 0.00141

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00553

Gnomad OTH AF: 0.00239

GnomAD4 exome AF: 0.00412 AC: 332 AN: 80596 Hom.: 1 Cov.: 0 AF XY: 0.00445 AC XY: 165 AN XY: 37078

Gnomad4 AFR exome AF: 0.000258

Gnomad4 AMR exome AF: 0.00322

Gnomad4 ASJ exome AF: 0.00118

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00573

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00577

Gnomad4 OTH exome AF: 0.00386

GnomAD4 genome AF: 0.00342 AC: 521 AN: 152344 Hom.: 0 Cov.: 33 AF XY: 0.00333 AC XY: 248 AN XY: 74496

Gnomad4 AFR AF: 0.000914

Gnomad4 AMR AF: 0.00340

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00704

Gnomad4 FIN AF: 0.00141

Gnomad4 NFE AF: 0.00553

Gnomad4 OTH AF: 0.00236

Alfa AF: 0.00149 Hom.: 0

Bravo AF: 0.00304

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

May 04, 2022

- -

FOXL2-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 21, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2022

FOXL2: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	9.2
DANN	Benign	0.83

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: rs180829214; hg19: chr3-138663815;