Variant 16-86567443-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_005251.3(FOXC2):c.108C>T(p.Ser36=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00792 in 1,613,278 control chromosomes in the GnomAD database, including 72 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0064 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0081 ( 68 hom. )

Consequence

FOXC2
NM_005251.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.521

Variant links:

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 links:

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

FOXC2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 16-86567443-C-T is Benign according to our data. Variant chr16-86567443-C-T is described in ClinVar as [Benign]. Clinvar id is 259691.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-86567443-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.521 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0064 (975/152290) while in subpopulation NFE AF= 0.00987 (671/68016). AF 95% confidence interval is 0.00925. There are 4 homozygotes in gnomad4. There are 455 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 975 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXC2	NM_005251.3 linkuse as main transcript	c.108C>T	p.Ser36=	synonymous_variant	1/1	ENST00000649859.1
FOXC2-AS1	NR_125795.1 linkuse as main transcript	n.145+174G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXC2	ENST00000649859.1 linkuse as main transcript	c.108C>T	p.Ser36=	synonymous_variant	1/1		NM_005251.3	P1
FOXC2-AS1	ENST00000563280.3 linkuse as main transcript	n.231+174G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00641

AC:

975

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00261

Gnomad AMI

AF:

0.0164

Gnomad AMR

AF:

0.00772

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00310

Gnomad FIN

AF:

0.00122

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00986

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.00678

AC:

1694

AN:

249682

Hom.:

AF XY:

0.00715

AC XY:

968

AN XY:

135428

show subpopulations

Gnomad AFR exome

AF:

0.00195

Gnomad AMR exome

AF:

0.00530

Gnomad ASJ exome

AF:

0.00220

Gnomad EAS exome

AF:

0.0000546

Gnomad SAS exome

AF:

0.00226

Gnomad FIN exome

AF:

0.00314

Gnomad NFE exome

AF:

0.0113

Gnomad OTH exome

AF:

0.00852

GnomAD4 exome

AF:

0.00807

AC:

11796

AN:

1460988

Hom.:

Cov.:

AF XY:

0.00787

AC XY:

5717

AN XY:

726846

show subpopulations

Gnomad4 AFR exome

AF:

0.00218

Gnomad4 AMR exome

AF:

0.00564

Gnomad4 ASJ exome

AF:

0.00218

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00238

Gnomad4 FIN exome

AF:

0.00269

Gnomad4 NFE exome

AF:

0.00942

Gnomad4 OTH exome

AF:

0.00740

GnomAD4 genome

AF:

0.00640

AC:

975

AN:

152290

Hom.:

Cov.:

AF XY:

0.00611

AC XY:

455

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00260

Gnomad4 AMR

AF:

0.00771

Gnomad4 ASJ

AF:

0.00231

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00311

Gnomad4 FIN

AF:

0.00122

Gnomad4 NFE

AF:

0.00987

Gnomad4 OTH

AF:

0.00994

Alfa

AF:

0.00833

Hom.:

Bravo

AF:

0.00726

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.0115

EpiControl

AF:

0.0134

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Jul 30, 2020	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2024	FOXC2: BP4, BP7, BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 05, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.97

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over