rs61750361

chr3-138946222-G-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_023067.4(FOXL2):c.501C>T(p.Phe167=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0408 in 1,537,794 control chromosomes in the GnomAD database, including 4,959 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (2227 hom., cov: 33)
  • Exomes 𝑓: 0.033 (2732 hom.)
• Consequence: FOXL2 NM_023067.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.0650

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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 3-138946222-G-A is Benign according to our data. Variant chr3-138946222-G-A is described in ClinVar as [Benign]. Clinvar id is 261661.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.065 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXL2	NM_023067.4	c.501C>T	p.Phe167=	synonymous_variant	1/1	ENST00000648323.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXL2	ENST00000648323.1	c.501C>T	p.Phe167=	synonymous_variant	1/1		NM_023067.4	P1

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17065 AN: 151604 Hom.: 2215 Cov.: 33

Gnomad AFR AF: 0.321

Gnomad AMI AF: 0.0286

Gnomad AMR AF: 0.0521

Gnomad ASJ AF: 0.0294

Gnomad EAS AF: 0.0297

Gnomad SAS AF: 0.0853

Gnomad FIN AF: 0.0627

Gnomad MID AF: 0.0613

Gnomad NFE AF: 0.0214

Gnomad OTH AF: 0.0924

GnomAD3 exomes AF: 0.0501 AC: 6865 AN: 136944 Hom.: 500 AF XY: 0.0512 AC XY: 3868 AN XY: 75494

Gnomad AFR exome AF: 0.355

Gnomad AMR exome AF: 0.0255

Gnomad ASJ exome AF: 0.0215

Gnomad EAS exome AF: 0.0129

Gnomad SAS exome AF: 0.0892

Gnomad FIN exome AF: 0.0598

Gnomad NFE exome AF: 0.0223

Gnomad OTH exome AF: 0.0429

GnomAD4 exome AF: 0.0329 AC: 45616 AN: 1386086 Hom.: 2732 Cov.: 32 AF XY: 0.0341 AC XY: 23317 AN XY: 684396

Gnomad4 AFR exome AF: 0.342

Gnomad4 AMR exome AF: 0.0288

Gnomad4 ASJ exome AF: 0.0237

Gnomad4 EAS exome AF: 0.0671

Gnomad4 SAS exome AF: 0.0880

Gnomad4 FIN exome AF: 0.0542

Gnomad4 NFE exome AF: 0.0177

Gnomad4 OTH exome AF: 0.0464

GnomAD4 genome AF: 0.113 AC: 17131 AN: 151708 Hom.: 2227 Cov.: 33 AF XY: 0.112 AC XY: 8316 AN XY: 74164

Gnomad4 AFR AF: 0.321

Gnomad4 AMR AF: 0.0521

Gnomad4 ASJ AF: 0.0294

Gnomad4 EAS AF: 0.0298

Gnomad4 SAS AF: 0.0852

Gnomad4 FIN AF: 0.0627

Gnomad4 NFE AF: 0.0214

Gnomad4 OTH AF: 0.0986

Alfa AF: 0.0531 Hom.: 181

Bravo AF: 0.118

Asia WGS AF: 0.0820 AC: 288 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Mar 14, 2017	- -

Blepharophimosis, ptosis, and epicanthus inversus syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Nov 03, 2016

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
Cadd	Benign	11
Dann	Benign	0.97

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: rs61750361; hg19: chr3-138665064;