dbSNP rs987237: TFAP2B:c.602-724A>G (chr6-50835337-A-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is . The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_003221.4(TFAP2B):c.602-724A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 152,228 control chromosomes in the GnomAD database, including 2,544 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.17 ( 2544 hom., cov: 33)

Consequence

TFAP2B
NM_003221.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.12

Publications

218 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, Orphanet, PanelApp Australia, 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:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_003221.4, 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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.23).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFAP2B	NM_003221.4	MANE Select	c.602-724A>G		intron	N/A	NP_003212.2	Q92481-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFAP2B	ENST00000393655.4	TSL:1 MANE Select	c.602-724A>G		intron	N/A	ENSP00000377265.2	Q92481-1

Frequencies

GnomAD3 genomes

AF:

0.172

AC:

26228

AN:

152112

Hom.:

2544

Cov.:

show subpopulations

Gnomad AFR

AF:

0.102

Gnomad AMI

AF:

0.125

Gnomad AMR

AF:

0.280

Gnomad ASJ

AF:

0.156

Gnomad EAS

AF:

0.164

Gnomad SAS

AF:

0.218

Gnomad FIN

AF:

0.194

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.186

Gnomad OTH

AF:

0.189

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.172

AC:

26236

AN:

152228

Hom.:

2544

Cov.:

AF XY:

0.174

AC XY:

12967

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.102

AC:

4230

AN:

41540

American (AMR)

AF:

0.280

AC:

4285

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.156

AC:

543

AN:

3472

East Asian (EAS)

AF:

0.164

AC:

851

AN:

5188

South Asian (SAS)

AF:

0.218

AC:

1053

AN:

4822

European-Finnish (FIN)

AF:

0.194

AC:

2057

AN:

10600

Middle Eastern (MID)

AF:

0.153

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.186

AC:

12662

AN:

67996

Other (OTH)

AF:

0.188

AC:

396

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1112

2224

3337

4449

5561

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

292

584

876

1168

1460

<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:

0.185

Hom.:

12068

Bravo

AF:

0.178

Asia WGS

AF:

0.228

AC:

793

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.23

CADD

Benign

(source)

DANN

Benign

0.74

PhyloP100

1.1

Mutation Taster

=100/0

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over