chr16-86577785-T-G

Variant names:

• chr16-86577785-T-G
• rs34152738
• ENST00000593625.1:c.-162-777T>G

Variant summary

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

The ENST00000593625.1(FOXL1):​c.-162-777T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 152,048 control chromosomes in the GnomAD database, including 8,323 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 0.31 (8323 hom., cov: 33)
• Consequence: FOXL1 ENST00000593625.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.927
• Publications: 4 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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000593625.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXL1	ENST00000593625.1	TSL:5	c.-162-777T>G		intron	N/A	ENSP00000472376.1
	ENSG00000261161	ENST00000808928.1		n.120+4597T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46698 AN: 151930 Hom.: 8308 Cov.: 33

Gnomad AFR AF: 0.447

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.258

Gnomad EAS AF: 0.519

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.287

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

GnomAD4 genome AF: 0.308 AC: 46770 AN: 152048 Hom.: 8323 Cov.: 33 AF XY: 0.313 AC XY: 23251 AN XY: 74304

African (AFR) AF: 0.448 AC: 18557 AN: 41468

American (AMR) AF: 0.392 AC: 5990 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.258 AC: 896 AN: 3472

East Asian (EAS) AF: 0.520 AC: 2670 AN: 5136

South Asian (SAS) AF: 0.350 AC: 1686 AN: 4822

European-Finnish (FIN) AF: 0.205 AC: 2166 AN: 10580

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.203 AC: 13825 AN: 67964

Other (OTH) AF: 0.285 AC: 602 AN: 2114

Alfa AF: 0.243 Hom.: 13099

Bravo AF: 0.328

Asia WGS AF: 0.413 AC: 1437 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	3.2
DANN	Benign	0.66
PhyloP100		-0.93

Splicing

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

Other links and lift over

dbSNP: rs34152738; hg19: chr16-86611391;