ENST00000563280.4:n.313+793G>A

Variant names:

• chr16-86566824-C-T
• rs34221221
• ENST00000563280.4:n.313+793G>A

Variant summary

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

The ENST00000563280.4(FOXC2-AS1):​n.313+793G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 152,082 control chromosomes in the GnomAD database, including 19,946 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 0.49 (19946 hom., cov: 33)
• Consequence: FOXC2-AS1 ENST00000563280.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.551
• Publications: 31 publications found

Genes affected

FOXC2-AS1 (HGNC:50665): (FOXC2 antisense RNA 1)

FOXC2 (HGNC:3801): (forkhead box C2) This gene belongs to the forkhead family of transcription factors which is characterized by a distinct DNA-binding forkhead domain. The specific function of this gene has not yet been determined; however, it may play a role in the development of mesenchymal tissues. [provided by RefSeq, Jul 2008]

FOXC2 Gene-Disease associations (from GenCC):

• lymphedema-distichiasis syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: G2P, Genomics England PanelApp, ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.616 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000563280.4. 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
	FOXC2-AS1	NR_125795.1		n.145+793G>A		intron	N/A
	FOXC2	NM_005251.3	MANE Select	c.-512C>T		upstream_gene	N/A	NP_005242.1	Q99958

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXC2-AS1	ENST00000563280.4	TSL:3	n.313+793G>A		intron	N/A
	FOXC2-AS1	ENST00000809048.1		n.63-1506G>A		intron	N/A
	FOXC2-AS1	ENST00000809049.1		n.300+566G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.491 AC: 74620 AN: 151966 Hom.: 19953 Cov.: 33

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.484

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.362

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.615

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.621

Gnomad OTH AF: 0.518

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

GnomAD4 genome AF: 0.491 AC: 74615 AN: 152082 Hom.: 19946 Cov.: 33 AF XY: 0.488 AC XY: 36271 AN XY: 74360

African (AFR) AF: 0.281 AC: 11684 AN: 41520

American (AMR) AF: 0.447 AC: 6838 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.501 AC: 1739 AN: 3468

East Asian (EAS) AF: 0.362 AC: 1861 AN: 5140

South Asian (SAS) AF: 0.449 AC: 2167 AN: 4826

European-Finnish (FIN) AF: 0.615 AC: 6492 AN: 10564

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.621 AC: 42172 AN: 67964

Other (OTH) AF: 0.514 AC: 1084 AN: 2108

Alfa AF: 0.559 Hom.: 4299

Bravo AF: 0.468

Asia WGS AF: 0.409 AC: 1422 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	19
DANN	Benign	0.93
PhyloP100		0.55
PromoterAI		-0.15	Neutral

Splicing

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

Other links and lift over

dbSNP: rs34221221; hg19: chr16-86600430;