NM_005250.3:c.*3519G>A

Variant names:

• chr16-86583280-G-A
• rs12711457
• NM_005250.3:c.*3519G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

FOXL1 Gene-Disease associations (from GenCC):

• otosclerosis 11

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• congenital heart disease

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ENSG00000261161 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005250.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXL1	NM_005250.3	MANE Select	c.*3519G>A		3_prime_UTR	Exon 1 of 1	NP_005241.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXL1	ENST00000320241.5	TSL:6 MANE Select	c.*3519G>A		3_prime_UTR	Exon 1 of 1	ENSP00000326272.3
	ENSG00000261161	ENST00000808928.1		n.120+10092G>A		intron	N/A

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

African (AFR) AF: 0.683 AC: 28175 AN: 41252

American (AMR) AF: 0.502 AC: 7633 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.455 AC: 1577 AN: 3468

East Asian (EAS) AF: 0.698 AC: 3598 AN: 5154

South Asian (SAS) AF: 0.446 AC: 2128 AN: 4770

European-Finnish (FIN) AF: 0.475 AC: 4969 AN: 10462

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.393 AC: 26659 AN: 67878

Other (OTH) AF: 0.483 AC: 1014 AN: 2100

Alfa AF: 0.448 Hom.: 28082

Bravo AF: 0.520

Asia WGS AF: 0.567 AC: 1972 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.10
DANN	Benign	0.43
PhyloP100		-2.1

Splicing

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

Other links and lift over

dbSNP: rs12711457; hg19: chr16-86616886;