rs34221221

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr16-86566824-C-G
• chr16-86566824-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000563280.4(FOXC2-AS1):​n.313+793G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).

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>C		intron	N/A
	FOXC2	NM_005251.3	MANE Select	c.-512C>G		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>C		intron	N/A
	FOXC2-AS1	ENST00000809048.1		n.63-1506G>C		intron	N/A
	FOXC2-AS1	ENST00000809049.1		n.300+566G>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 4299

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	19
DANN	Benign	0.81
PhyloP100		0.55
PromoterAI		0.12	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;