6-50823871-CACAAACAAACAA-CACAAACAA

Variant names:

• chr6-50823871-CACAA-C
• rs368226832
• NM_003221.4:c.540+28_540+31delCAAA

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_003221.4(TFAP2B):​c.540+28_540+31delCAAA variant causes a 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. 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 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 2.31
• Publications: 0 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 258985.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TFAP2B	NM_003221.4	c.540+28_540+31delCAAA		intron_variant	Intron 2 of 6	ENST00000393655.4	NP_003212.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TFAP2B	ENST00000393655.4	c.540+7_540+10delACAA		splice_region_variant, intron_variant	Intron 2 of 6	1	NM_003221.4	ENSP00000377265.2
TFAP2B	ENST00000344788.7	c.534+7_534+10delACAA		splice_region_variant, intron_variant	Intron 3 of 3	3		ENSP00000342252.3
TFAP2B	ENST00000489228.1	n.*7_*10delACAA		downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.470 AC: 71100 AN: 151176 Hom.: 18724 Cov.: 0

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

GnomAD2 exomes AF: 0.377 AC: 51128 AN: 135480 AF XY: 0.381

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 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

African (AFR) AF: 0.747 AC: 23343 AN: 31268

American (AMR) AF: 0.291 AC: 10471 AN: 35924

Ashkenazi Jewish (ASJ) AF: 0.422 AC: 10616 AN: 25148

East Asian (EAS) AF: 0.318 AC: 11390 AN: 35816

South Asian (SAS) AF: 0.412 AC: 32639 AN: 79260

European-Finnish (FIN) AF: 0.371 AC: 14237 AN: 38328

Middle Eastern (MID) AF: 0.482 AC: 2740 AN: 5686

European-Non Finnish (NFE) AF: 0.356 AC: 383549 AN: 1077332

Other (OTH) AF: 0.392 AC: 22691 AN: 57910

GnomAD4 genome AF: 0.471 AC: 71195 AN: 151292 Hom.: 18763 Cov.: 0 AF XY: 0.469 AC XY: 34652 AN XY: 73856

African (AFR) AF: 0.737 AC: 30295 AN: 41098

American (AMR) AF: 0.371 AC: 5646 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.436 AC: 1506 AN: 3458

East Asian (EAS) AF: 0.329 AC: 1682 AN: 5112

South Asian (SAS) AF: 0.411 AC: 1965 AN: 4784

European-Finnish (FIN) AF: 0.403 AC: 4215 AN: 10448

Middle Eastern (MID) AF: 0.490 AC: 142 AN: 290

European-Non Finnish (NFE) AF: 0.361 AC: 24485 AN: 67878

Other (OTH) AF: 0.461 AC: 969 AN: 2100

Alfa AF: 0.295 Hom.: 1042

Bravo AF: 0.481

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

May 20, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Char syndrome Benign:1

Sep 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs368226832; hg19: chr6-50791584;