16-86566824-C-T

Position:

• chr16-86566824-C-T

Variant summary

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

The ENST00000563280.3(FOXC2-AS1):​n.231+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 ENST00000563280.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.551

Genes affected

FOXC2-AS1 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXC2-AS1	NR_125795.1	n.145+793G>A		intron_variant
FOXC2	NM_005251.3	c.-512C>T		upstream_gene_variant		ENST00000649859.1	NP_005242.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXC2-AS1	ENST00000563280.3	n.231+793G>A		intron_variant		3
FOXC2	ENST00000649859.1	c.-512C>T		upstream_gene_variant			NM_005251.3	ENSP00000497759.1

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

Gnomad4 AFR AF: 0.281

Gnomad4 AMR AF: 0.447

Gnomad4 ASJ AF: 0.501

Gnomad4 EAS AF: 0.362

Gnomad4 SAS AF: 0.449

Gnomad4 FIN AF: 0.615

Gnomad4 NFE AF: 0.621

Gnomad4 OTH AF: 0.514

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	19
DANN	Benign	0.93

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs34221221; hg19: chr16-86600430;