rs78816814

Variant names:

• chr16-86566986-G-T
• rs78816814
• NM_005251.3:c.-350G>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005251.3(FOXC2):​c.-350G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0436 in 151,724 control chromosomes in the GnomAD database, including 330 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.044 (330 hom., cov: 33)
• Consequence: FOXC2 NM_005251.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.184
• Publications: 3 publications found

Genes affected

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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 16-86566986-G-T is Benign according to our data. Variant chr16-86566986-G-T is described in ClinVar as Benign. ClinVar VariationId is 1245191.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005251.3. 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	NM_005251.3	MANE Select	c.-350G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 1	NP_005242.1	Q99958
	FOXC2	NM_005251.3	MANE Select	c.-350G>T		5_prime_UTR	Exon 1 of 1	NP_005242.1	Q99958
	FOXC2-AS1	NR_125795.1		n.145+631C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXC2	ENST00000649859.1	MANE Select	c.-350G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 1	ENSP00000497759.1	Q99958
	FOXC2	ENST00000649859.1	MANE Select	c.-350G>T		5_prime_UTR	Exon 1 of 1	ENSP00000497759.1	Q99958
	FOXC2-AS1	ENST00000563280.4	TSL:3	n.313+631C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0435 AC: 6596 AN: 151616 Hom.: 329 Cov.: 33

Gnomad AFR AF: 0.0700

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0823

Gnomad ASJ AF: 0.00809

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.0586

Gnomad FIN AF: 0.0438

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.00671

Gnomad OTH AF: 0.0362

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

GnomAD4 genome AF: 0.0436 AC: 6619 AN: 151724 Hom.: 330 Cov.: 33 AF XY: 0.0471 AC XY: 3492 AN XY: 74136

African (AFR) AF: 0.0701 AC: 2909 AN: 41478

American (AMR) AF: 0.0829 AC: 1264 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.00809 AC: 28 AN: 3462

East Asian (EAS) AF: 0.220 AC: 1127 AN: 5122

South Asian (SAS) AF: 0.0588 AC: 284 AN: 4826

European-Finnish (FIN) AF: 0.0438 AC: 458 AN: 10456

Middle Eastern (MID) AF: 0.0103 AC: 3 AN: 292

European-Non Finnish (NFE) AF: 0.00671 AC: 455 AN: 67836

Other (OTH) AF: 0.0358 AC: 75 AN: 2096

Alfa AF: 0.0250 Hom.: 11

Bravo AF: 0.0483

Asia WGS AF: 0.114 AC: 394 AN: 3464

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.2
DANN	Benign	0.91
PhyloP100		-0.18
PromoterAI		0.079	Neutral

Splicing

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

Other links and lift over

dbSNP: rs78816814; hg19: chr16-86600592;