6-50823871-CACAAACAAACAA-CACAAACAAACAAACAA

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6BS1BS2

The NM_003221.4(TFAP2B):c.540+28_540+31dupCAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0025 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0011 ( 11 hom. )

Consequence

TFAP2B
NM_003221.4 intron

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:3

Conservation

PhyloP100: 0.0710

Publications

0 publications found

Variant links:

Genes affected

TFAP2B (HGNC:11743): (transcription factor AP-2 beta) This gene encodes a member of the AP-2 family of transcription factors. AP-2 proteins form homo- or hetero-dimers with other AP-2 family members and bind specific DNA sequences. They are thought to stimulate cell proliferation and suppress terminal differentiation of specific cell types during embryonic development. Specific AP-2 family members differ in their expression patterns and binding affinity for different promoters. This protein functions as both a transcriptional activator and repressor. Mutations in this gene result in autosomal dominant Char syndrome, suggesting that this gene functions in the differentiation of neural crest cell derivatives. [provided by RefSeq, Jul 2008]

TFAP2B Gene-Disease associations (from GenCC):

Char syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet
familial patent arterial duct
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

TFAP2B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP6

Variant 6-50823871-C-CACAA is Benign according to our data. Variant chr6-50823871-C-CACAA is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 357277.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00252 (382/151390) while in subpopulation AFR AF = 0.00525 (216/41122). AF 95% confidence interval is 0.00468. There are 0 homozygotes in GnomAd4. There are 184 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High AC in GnomAd4 at 382 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003221.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFAP2B	NM_003221.4	MANE Select	c.540+28_540+31dupCAAA		intron	N/A	NP_003212.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TFAP2B	ENST00000393655.4	TSL:1 MANE Select	c.540+6_540+7insACAA	splice_region intron	N/A	ENSP00000377265.2
TFAP2B	ENST00000344788.7	TSL:3	c.534+6_534+7insACAA	splice_region intron	N/A	ENSP00000342252.3
TFAP2B	ENST00000489228.1	TSL:2	n.6_7insACAA	downstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.00250

AC:

378

AN:

151274

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00517

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000920

Gnomad ASJ

AF:

0.0309

Gnomad EAS

AF:

0.000390

Gnomad SAS

AF:

0.000417

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00321

Gnomad NFE

AF:

0.000515

Gnomad OTH

AF:

0.00240

GnomAD2 exomes

AF:

0.00289

AC:

392

AN:

135480

AF XY:

0.00274

show subpopulations

Gnomad AFR exome

AF:

0.00488

Gnomad AMR exome

AF:

0.000892

Gnomad ASJ exome

AF:

0.0338

Gnomad EAS exome

AF:

0.000555

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000749

Gnomad OTH exome

AF:

0.00341

GnomAD4 exome

AF:

0.00114

AC:

1588

AN:

1387008

Hom.:

Cov.:

AF XY:

0.00116

AC XY:

796

AN XY:

684848

show subpopulations

African (AFR)

AF:

0.00572

AC:

179

AN:

31270

American (AMR)

AF:

0.000891

AC:

AN:

35926

Ashkenazi Jewish (ASJ)

AF:

0.0321

AC:

807

AN:

25152

East Asian (EAS)

AF:

0.000112

AC:

AN:

35816

South Asian (SAS)

AF:

0.000290

AC:

AN:

79280

European-Finnish (FIN)

AF:

0.0000261

AC:

AN:

38342

Middle Eastern (MID)

AF:

0.00106

AC:

AN:

5686

European-Non Finnish (NFE)

AF:

0.000353

AC:

380

AN:

1077620

Other (OTH)

AF:

0.00269

AC:

156

AN:

57916

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

180

270

360

450

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

150

<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:

0.00252

AC:

382

AN:

151390

Hom.:

Cov.:

AF XY:

0.00249

AC XY:

184

AN XY:

73918

show subpopulations

African (AFR)

AF:

0.00525

AC:

216

AN:

41122

American (AMR)

AF:

0.000919

AC:

AN:

15232

Ashkenazi Jewish (ASJ)

AF:

0.0309

AC:

107

AN:

3458

East Asian (EAS)

AF:

0.000391

AC:

AN:

5120

South Asian (SAS)

AF:

0.000417

AC:

AN:

4792

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10466

Middle Eastern (MID)

AF:

0.00345

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.000515

AC:

AN:

67900

Other (OTH)

AF:

0.00238

AC:

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00623

Hom.:

1042

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Benign:3

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Dec 10, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Char syndrome

Uncertain:2

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.071

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over