XM_017011233.2:c.59G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 1P and 18B. PP2BP4_ModerateBP6_Very_StrongBA1

The XM_017011233.2(TFAP2B):c.59G>A(p.Ser20Asn) variant causes a missense change. The variant allele was found at a frequency of 0.126 in 1,600,400 control chromosomes in the GnomAD database, including 15,106 homozygotes. In-silico tool predicts a benign outcome for this variant. 4/5 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2795 hom., cov: 32)

Exomes 𝑓: 0.12 ( 12311 hom. )

Consequence

TFAP2B
XM_017011233.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 6.23

Publications

21 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: PanelApp Australia, G2P, Orphanet, Labcorp Genetics (formerly Invitae)
TFAP2B-related congenital heart disease spectrum disorder
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
patent ductus arteriosus 2
Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia
familial patent arterial duct
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

TFAP2B links:

ENSG00000297125 (HGNC:):

ENSG00000297125 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript XM_017011233.2, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 8 curated pathogenic missense variants (we use a threshold of 10). The gene has 2 curated benign missense variants. Gene score misZ: 1.2875 (below the threshold of 3.09). Trascript score misZ: 1.5192 (below the threshold of 3.09). GenCC associations: The gene is linked to familial patent arterial duct, Char syndrome, TFAP2B-related congenital heart disease spectrum disorder, patent ductus arteriosus 2.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 6-50818858-G-A is Benign according to our data. Variant chr6-50818858-G-A is described in ClinVar as Benign. ClinVar VariationId is 1273651.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000393655.4. 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
	TFAP2B	NM_003221.4	MANE Select	c.-34G>A		upstream_gene	N/A	NP_003212.2	Q92481-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TFAP2B	ENST00000344788.7	TSL:3	c.-67G>A	5_prime_UTR	Exon 1 of 4	ENSP00000342252.3	X6R4Y8
ENSG00000297125	ENST00000745639.1		n.343+44C>T	intron	N/A
TFAP2B	ENST00000393655.4	TSL:1 MANE Select	c.-34G>A	upstream_gene	N/A	ENSP00000377265.2	Q92481-1

Frequencies

GnomAD3 genomes

AF:

0.173

AC:

26273

AN:

151822

Hom.:

2792

Cov.:

show subpopulations

Gnomad AFR

AF:

0.291

Gnomad AMI

AF:

0.0681

Gnomad AMR

AF:

0.145

Gnomad ASJ

AF:

0.176

Gnomad EAS

AF:

0.208

Gnomad SAS

AF:

0.192

Gnomad FIN

AF:

0.192

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.102

Gnomad OTH

AF:

0.169

GnomAD2 exomes

AF:

0.149

AC:

37476

AN:

250704

AF XY:

0.149

show subpopulations

Gnomad AFR exome

AF:

0.295

Gnomad AMR exome

AF:

0.118

Gnomad ASJ exome

AF:

0.171

Gnomad EAS exome

AF:

0.228

Gnomad FIN exome

AF:

0.187

Gnomad NFE exome

AF:

0.105

Gnomad OTH exome

AF:

0.154

GnomAD4 exome

AF:

0.122

AC:

176025

AN:

1448460

Hom.:

12311

Cov.:

AF XY:

0.123

AC XY:

88848

AN XY:

721588

show subpopulations

African (AFR)

AF:

0.299

AC:

9910

AN:

33184

American (AMR)

AF:

0.121

AC:

5423

AN:

44690

Ashkenazi Jewish (ASJ)

AF:

0.167

AC:

4345

AN:

26054

East Asian (EAS)

AF:

0.226

AC:

8936

AN:

39618

South Asian (SAS)

AF:

0.189

AC:

16276

AN:

85952

European-Finnish (FIN)

AF:

0.175

AC:

9327

AN:

53158

Middle Eastern (MID)

AF:

0.163

AC:

937

AN:

5740

European-Non Finnish (NFE)

AF:

0.102

AC:

112690

AN:

1100116

Other (OTH)

AF:

0.136

AC:

8181

AN:

59948

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

7736

15471

23207

30942

38678

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4428

8856

13284

17712

22140

<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:

0.173

AC:

26288

AN:

151940

Hom.:

2795

Cov.:

AF XY:

0.179

AC XY:

13294

AN XY:

74268

show subpopulations

African (AFR)

AF:

0.290

AC:

12013

AN:

41382

American (AMR)

AF:

0.146

AC:

2230

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.176

AC:

611

AN:

3470

East Asian (EAS)

AF:

0.207

AC:

1068

AN:

5154

South Asian (SAS)

AF:

0.192

AC:

920

AN:

4802

European-Finnish (FIN)

AF:

0.192

AC:

2028

AN:

10558

Middle Eastern (MID)

AF:

0.160

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.102

AC:

6955

AN:

67978

Other (OTH)

AF:

0.168

AC:

354

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1051

2102

3153

4204

5255

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

276

552

828

1104

1380

<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:

0.132

Hom.:

3401

Bravo

AF:

0.175

Asia WGS

AF:

0.182

AC:

632

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Char syndrome (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Benign

0.93

PhyloP100

6.2

PromoterAI

0.042

Neutral

(source)

Mutation Taster

=299/1

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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