NM_023067.4:c.-251G>C

Variant names:

• chr3-138946973-C-G
• rs145924266
• NM_023067.4:c.-251G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_023067.4(FOXL2):​c.-251G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000489 in 408,822 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000049 (0 hom.)
• Consequence: FOXL2 NM_023067.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.785
• Publications: 0 publications found

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]

FOXL2NB (HGNC:34428): (FOXL2 neighbor) Located in fibrillar center. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_023067.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXL2	NM_023067.4	MANE Select	c.-251G>C		5_prime_UTR	Exon 1 of 1	NP_075555.1	Q53ZD3
	FOXL2NB	NM_001040061.3	MANE Select	c.-392C>G		upstream_gene	N/A	NP_001035150.1	Q6ZUU3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXL2	ENST00000648323.1	MANE Select	c.-251G>C		5_prime_UTR	Exon 1 of 1	ENSP00000497217.1	P58012
	FOXL2NB	ENST00000383165.4	TSL:2 MANE Select	c.-392C>G		upstream_gene	N/A	ENSP00000372651.3	Q6ZUU3
	FOXL2NB	ENST00000959845.1		c.-392C>G		upstream_gene	N/A	ENSP00000629904.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000489 AC: 2 AN: 408822 Hom.: 0 Cov.: 5 AF XY: 0.00000471 AC XY: 1 AN XY: 212276

African (AFR) AF: 0.00 AC: 0 AN: 8634

American (AMR) AF: 0.00 AC: 0 AN: 12544

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12244

East Asian (EAS) AF: 0.00 AC: 0 AN: 25810

South Asian (SAS) AF: 0.00 AC: 0 AN: 33152

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37734

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1826

European-Non Finnish (NFE) AF: 0.00000790 AC: 2 AN: 253142

Other (OTH) AF: 0.00 AC: 0 AN: 23736

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	16
DANN	Benign	0.87
PhyloP100		0.79
PromoterAI		0.077	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs145924266; hg19: chr3-138665815;