Variant 6-50823871-CACAAACAAACAA-CACAAACAA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_003221.4(TFAP2B):c.540+28_540+31del variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 1,537,964 control chromosomes in the GnomAD database, including 116,547 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 18763 hom., cov: 0)

Exomes 𝑓: 0.37 ( 97784 hom. )

Consequence

TFAP2B
NM_003221.4 splice_region, intron

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 2.31

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 6-50823871-CACAA-C is Benign according to our data. Variant chr6-50823871-CACAA-C is described in ClinVar as [Benign]. Clinvar id is 258985.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-50823871-CACAA-C is described in Lovd as [Likely_benign]. Variant chr6-50823871-CACAA-C is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TFAP2B	NM_003221.4 linkuse as main transcript	c.540+28_540+31del		splice_region_variant, intron_variant		ENST00000393655.4

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
TFAP2B	ENST00000393655.4 linkuse as main transcript	c.540+28_540+31del	splice_region_variant, intron_variant	1	NM_003221.4	P1	Q92481-1
TFAP2B	ENST00000344788.7 linkuse as main transcript	c.534+28_534+31del	splice_region_variant, intron_variant	3
TFAP2B	ENST00000489228.1 linkuse as main transcript		downstream_gene_variant	2

Frequencies

GnomAD3 genomes

AF:

0.470

AC:

71100

AN:

151176

Hom.:

18724

Cov.:

show subpopulations

Gnomad AFR

AF:

0.737

Gnomad AMI

AF:

0.319

Gnomad AMR

AF:

0.371

Gnomad ASJ

AF:

0.436

Gnomad EAS

AF:

0.330

Gnomad SAS

AF:

0.411

Gnomad FIN

AF:

0.403

Gnomad MID

AF:

0.484

Gnomad NFE

AF:

0.361

Gnomad OTH

AF:

0.460

GnomAD3 exomes

AF:

0.377

AC:

51128

AN:

135480

Hom.:

10407

AF XY:

0.381

AC XY:

28134

AN XY:

73818

show subpopulations

Gnomad AFR exome

AF:

0.748

Gnomad AMR exome

AF:

0.278

Gnomad ASJ exome

AF:

0.426

Gnomad EAS exome

AF:

0.355

Gnomad SAS exome

AF:

0.411

Gnomad FIN exome

AF:

0.364

Gnomad NFE exome

AF:

0.362

Gnomad OTH exome

AF:

0.400

GnomAD4 exome

AF:

0.369

AC:

511676

AN:

1386672

Hom.:

97784

AF XY:

0.370

AC XY:

253409

AN XY:

684686

show subpopulations

Gnomad4 AFR exome

AF:

0.747

Gnomad4 AMR exome

AF:

0.291

Gnomad4 ASJ exome

AF:

0.422

Gnomad4 EAS exome

AF:

0.318

Gnomad4 SAS exome

AF:

0.412

Gnomad4 FIN exome

AF:

0.371

Gnomad4 NFE exome

AF:

0.356

Gnomad4 OTH exome

AF:

0.392

GnomAD4 genome

AF:

0.471

AC:

71195

AN:

151292

Hom.:

18763

Cov.:

AF XY:

0.469

AC XY:

34652

AN XY:

73856

show subpopulations

Gnomad4 AFR

AF:

0.737

Gnomad4 AMR

AF:

0.371

Gnomad4 ASJ

AF:

0.436

Gnomad4 EAS

AF:

0.329

Gnomad4 SAS

AF:

0.411

Gnomad4 FIN

AF:

0.403

Gnomad4 NFE

AF:

0.361

Gnomad4 OTH

AF:

0.461

Bravo

AF:

0.481

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 20, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Char syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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