Genetic Variant NM_005251.3:c.*260A>G (chr16-86569101-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.103

Publications

13 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

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.*260A>G		3_prime_UTR	Exon 1 of 1	NP_005242.1	Q99958

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXC2	ENST00000649859.1	MANE Select	c.*260A>G		3_prime_UTR	Exon 1 of 1	ENSP00000497759.1	Q99958
	FOXC2-AS1	ENST00000809048.1		n.-82T>C		upstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.908

AC:

138110

AN:

152114

Hom.:

62801

Cov.:

show subpopulations

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.:

AF XY:

0.899

AC XY:

202646

AN XY:

225398

show subpopulations

African (AFR)

AF:

0.949

AC:

11131

AN:

11726

American (AMR)

AF:

0.892

AC:

15767

AN:

17670

Ashkenazi Jewish (ASJ)

AF:

0.856

AC:

10909

AN:

12746

East Asian (EAS)

AF:

0.857

AC:

24065

AN:

28078

South Asian (SAS)

AF:

0.923

AC:

41004

AN:

44412

European-Finnish (FIN)

AF:

0.947

AC:

38587

AN:

40726

Middle Eastern (MID)

AF:

0.876

AC:

1573

AN:

1796

European-Non Finnish (NFE)

AF:

0.892

AC:

221538

AN:

248440

Other (OTH)

AF:

0.888

AC:

21381

AN:

24066

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

1924

3848

5773

7697

9621

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

862

1724

2586

3448

4310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.908

AC:

138230

AN:

152232

Hom.:

62862

Cov.:

AF XY:

0.909

AC XY:

67637

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.945

AC:

39277

AN:

41548

American (AMR)

AF:

0.885

AC:

13544

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.856

AC:

2968

AN:

3468

East Asian (EAS)

AF:

0.847

AC:

4381

AN:

5172

South Asian (SAS)

AF:

0.925

AC:

4454

AN:

4814

European-Finnish (FIN)

AF:

0.947

AC:

10046

AN:

10610

Middle Eastern (MID)

AF:

0.890

AC:

260

AN:

292

European-Non Finnish (NFE)

AF:

0.892

AC:

60634

AN:

68002

Other (OTH)

AF:

0.895

AC:

1891

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

659

1317

1976

2634

3293

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

904

1808

2712

3616

4520

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.895

Hom.:

190083

Bravo

AF:

0.904

Asia WGS

AF:

0.871

AC:

3031

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.98

(source)

DANN

Benign

0.50

PhyloP100

0.10

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over