rs11924939

Positions:

• chr3-138946954-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_023067.4(FOXL2):​c.-232G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 610,648 control chromosomes in the GnomAD database, including 11,713 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 0.15 (2347 hom., cov: 33)
  • Exomes 𝑓: 0.19 (9366 hom.)
• Consequence: FOXL2 NM_023067.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.402

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXL2	NM_023067.4	c.-232G>A		5_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.-232G>A		5_prime_UTR_variant	1/1		NM_023067.4	ENSP00000497217.1

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23083 AN: 152106 Hom.: 2347 Cov.: 33

Gnomad AFR AF: 0.0443

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.00155

Gnomad SAS AF: 0.0530

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.172

GnomAD4 exome AF: 0.185 AC: 85027 AN: 458424 Hom.: 9366 Cov.: 6 AF XY: 0.182 AC XY: 43272 AN XY: 237936

Gnomad4 AFR exome AF: 0.0454

Gnomad4 AMR exome AF: 0.131

Gnomad4 ASJ exome AF: 0.244

Gnomad4 EAS exome AF: 0.000334

Gnomad4 SAS exome AF: 0.0631

Gnomad4 FIN exome AF: 0.181

Gnomad4 NFE exome AF: 0.225

Gnomad4 OTH exome AF: 0.183

GnomAD4 genome AF: 0.152 AC: 23075 AN: 152224 Hom.: 2347 Cov.: 33 AF XY: 0.147 AC XY: 10964 AN XY: 74430

Gnomad4 AFR AF: 0.0442

Gnomad4 AMR AF: 0.145

Gnomad4 ASJ AF: 0.249

Gnomad4 EAS AF: 0.00155

Gnomad4 SAS AF: 0.0528

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.225

Gnomad4 OTH AF: 0.170

Alfa AF: 0.192 Hom.: 632

Bravo AF: 0.148

Asia WGS AF: 0.0270 AC: 94 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	17
DANN	Benign	0.95

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: rs11924939; hg19: chr3-138665796; COSMIC: COSV57728323; COSMIC: COSV57728323;