rs12711457

Positions:

• chr16-86583280-G-A
• chr16-86583280-G-T

Variant summary

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

The NM_005250.3(FOXL1):​c.*3519G>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 0.504 in 151,502 control chromosomes in the GnomAD database, including 20,490 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 0.50 (20490 hom., cov: 30)
• Consequence: FOXL1 NM_005250.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.13

Genes affected

FOXL1 (HGNC:3817): (forkhead box L1) This gene encodes a member of the forkhead/winged helix-box (FOX) family of transcription factors. FOX transcription factors are characterized by a distinct DNA-binding forkhead domain and play critical roles in the regulation of multiple processes including metabolism, cell proliferation and gene expression during ontogenesis. [provided by RefSeq, Nov 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXL1	NM_005250.3	c.*3519G>A		3_prime_UTR_variant	1/1	ENST00000320241.5	NP_005241.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXL1	ENST00000320241.5	c.*3519G>A		3_prime_UTR_variant	1/1		NM_005250.3	ENSP00000326272	P1

Frequencies

GnomAD3 genomes AF: 0.504 AC: 76304 AN: 151384 Hom.: 20454 Cov.: 30

Gnomad AFR AF: 0.683

Gnomad AMI AF: 0.547

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.699

Gnomad SAS AF: 0.448

Gnomad FIN AF: 0.475

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.482

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.504 AC: 76397 AN: 151502 Hom.: 20490 Cov.: 30 AF XY: 0.507 AC XY: 37508 AN XY: 74002

Gnomad4 AFR AF: 0.683

Gnomad4 AMR AF: 0.502

Gnomad4 ASJ AF: 0.455

Gnomad4 EAS AF: 0.698

Gnomad4 SAS AF: 0.446

Gnomad4 FIN AF: 0.475

Gnomad4 NFE AF: 0.393

Gnomad4 OTH AF: 0.483

Alfa AF: 0.447 Hom.: 4192

Bravo AF: 0.520

Asia WGS AF: 0.567 AC: 1972 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.10
DANN	Benign	0.43

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12711457; hg19: chr16-86616886;