16-86569101-A-G

Position:

• chr16-86569101-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005251.3(FOXC2):​c.*260A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.901 in 581,892 control chromosomes in the GnomAD database, including 236,365 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.91 (62862 hom., cov: 32)
  • Exomes 𝑓: 0.90 (173503 hom.)
• Consequence: FOXC2 NM_005251.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.103

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 16-86569101-A-G is Benign according to our data. Variant chr16-86569101-A-G is described in ClinVar as [Benign]. Clinvar id is 1294075.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.938 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXC2	NM_005251.3	c.*260A>G		3_prime_UTR_variant	1/1	ENST00000649859.1	NP_005242.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXC2	ENST00000649859.1	c.*260A>G		3_prime_UTR_variant	1/1		NM_005251.3	ENSP00000497759	P1

Frequencies

GnomAD3 genomes AF: 0.908 AC: 138110 AN: 152114 Hom.: 62801 Cov.: 32

Gnomad AFR AF: 0.945

Gnomad AMI AF: 0.850

Gnomad AMR AF: 0.885

Gnomad ASJ AF: 0.856

Gnomad EAS AF: 0.847

Gnomad SAS AF: 0.924

Gnomad FIN AF: 0.947

Gnomad MID AF: 0.895

Gnomad NFE AF: 0.892

Gnomad OTH AF: 0.893

GnomAD4 exome AF: 0.898 AC: 385955 AN: 429660 Hom.: 173503 Cov.: 4 AF XY: 0.899 AC XY: 202646 AN XY: 225398

Gnomad4 AFR exome AF: 0.949

Gnomad4 AMR exome AF: 0.892

Gnomad4 ASJ exome AF: 0.856

Gnomad4 EAS exome AF: 0.857

Gnomad4 SAS exome AF: 0.923

Gnomad4 FIN exome AF: 0.947

Gnomad4 NFE exome AF: 0.892

Gnomad4 OTH exome AF: 0.888

GnomAD4 genome AF: 0.908 AC: 138230 AN: 152232 Hom.: 62862 Cov.: 32 AF XY: 0.909 AC XY: 67637 AN XY: 74414

Gnomad4 AFR AF: 0.945

Gnomad4 AMR AF: 0.885

Gnomad4 ASJ AF: 0.856

Gnomad4 EAS AF: 0.847

Gnomad4 SAS AF: 0.925

Gnomad4 FIN AF: 0.947

Gnomad4 NFE AF: 0.892

Gnomad4 OTH AF: 0.895

Alfa AF: 0.893 Hom.: 87934

Bravo AF: 0.904

Asia WGS AF: 0.871 AC: 3031 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 04, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.98
DANN	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1035550; hg19: chr16-86602707;