3-138944141-T-C

Variant names:

• chr3-138944141-T-C
• rs2291252
• NM_023067.4:c.*1451A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_023067.4(FOXL2):​c.*1451A>G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 197,238 control chromosomes in the GnomAD database, including 3,534 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 0.098 (2127 hom., cov: 33)
  • Exomes 𝑓: 0.12 (1407 hom.)
• Consequence: FOXL2 NM_023067.4 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.797
• Publications: 3 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]

LINC01391 (HGNC:50666): (long intergenic non-protein coding RNA 1391)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.545 is higher than 0.05.

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.*1451A>G		downstream_gene	N/A	NP_075555.1	Q53ZD3
	LINC01391	NR_121649.1		n.-121A>G		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXL2	ENST00000648323.1	MANE Select	c.*1451A>G		downstream_gene	N/A	ENSP00000497217.1	P58012
	LINC01391	ENST00000477059.2	TSL:3	n.-127A>G		upstream_gene	N/A
	LINC01391	ENST00000483650.1	TSL:3	n.-138A>G		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.0983 AC: 14947 AN: 152132 Hom.: 2124 Cov.: 33

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0471

Gnomad ASJ AF: 0.0352

Gnomad EAS AF: 0.564

Gnomad SAS AF: 0.0548

Gnomad FIN AF: 0.0274

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.00631

Gnomad OTH AF: 0.0827

GnomAD4 exome AF: 0.119 AC: 5366 AN: 44988 Hom.: 1407 Cov.: 0 AF XY: 0.116 AC XY: 2422 AN XY: 20950

African (AFR) AF: 0.219 AC: 391 AN: 1782

American (AMR) AF: 0.0376 AC: 44 AN: 1170

Ashkenazi Jewish (ASJ) AF: 0.0322 AC: 93 AN: 2890

East Asian (EAS) AF: 0.603 AC: 4413 AN: 7318

South Asian (SAS) AF: 0.0500 AC: 19 AN: 380

European-Finnish (FIN) AF: 0.0238 AC: 2 AN: 84

Middle Eastern (MID) AF: 0.0236 AC: 7 AN: 296

European-Non Finnish (NFE) AF: 0.00620 AC: 169 AN: 27250

Other (OTH) AF: 0.0597 AC: 228 AN: 3818

GnomAD4 genome AF: 0.0984 AC: 14986 AN: 152250 Hom.: 2127 Cov.: 33 AF XY: 0.100 AC XY: 7454 AN XY: 74458

African (AFR) AF: 0.242 AC: 10038 AN: 41518

American (AMR) AF: 0.0473 AC: 724 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0352 AC: 122 AN: 3470

East Asian (EAS) AF: 0.562 AC: 2909 AN: 5172

South Asian (SAS) AF: 0.0538 AC: 260 AN: 4834

European-Finnish (FIN) AF: 0.0274 AC: 291 AN: 10610

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.00631 AC: 429 AN: 68030

Other (OTH) AF: 0.0885 AC: 187 AN: 2114

Alfa AF: 0.0460 Hom.: 260

Bravo AF: 0.108

Asia WGS AF: 0.287 AC: 999 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	15
DANN	Benign	0.68
PhyloP100		0.80

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2291252; hg19: chr3-138662983;