6-50823871-CACAAACAAACAA-CACAA

Variant names:

• chr6-50823871-CACAAACAA-C
• rs368226832
• NM_003221.4:c.540+24_540+31delCAAACAAA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_003221.4(TFAP2B):​c.540+24_540+31delCAAACAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000093 in 1,537,944 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000089 (1 hom.)
• Consequence: TFAP2B NM_003221.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant 6-50823871-CACAAACAA-C is Benign according to our data. Variant chr6-50823871-CACAAACAA-C is described in ClinVar as Benign. ClinVar VariationId is 1608032.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000126 (19/151274) while in subpopulation AMR AF = 0.00112 (17/15212). AF 95% confidence interval is 0.000711. There are 0 homozygotes in GnomAd4. There are 7 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High AC in GnomAd4 at 19 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+24_540+31delCAAACAAA		intron	N/A	NP_003212.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFAP2B	ENST00000393655.4	TSL:1 MANE Select	c.540+7_540+14delACAAACAA		splice_region intron	N/A	ENSP00000377265.2
	TFAP2B	ENST00000344788.7	TSL:3	c.534+7_534+14delACAAACAA		splice_region intron	N/A	ENSP00000342252.3
	TFAP2B	ENST00000489228.1	TSL:2	n.*7_*14delACAAACAA		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.000126 AC: 19 AN: 151274 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000244

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00112

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000481

GnomAD2 exomes AF: 0.000642 AC: 87 AN: 135480 AF XY: 0.000528

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00337

Gnomad ASJ exome AF: 0.000366

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000244

GnomAD4 exome AF: 0.0000894 AC: 124 AN: 1386670 Hom.: 1 AF XY: 0.0000876 AC XY: 60 AN XY: 684718

African (AFR) AF: 0.0000320 AC: 1 AN: 31210

American (AMR) AF: 0.00278 AC: 100 AN: 35924

Ashkenazi Jewish (ASJ) AF: 0.000278 AC: 7 AN: 25150

East Asian (EAS) AF: 0.00 AC: 0 AN: 35812

South Asian (SAS) AF: 0.0000252 AC: 2 AN: 79278

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38334

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5686

European-Non Finnish (NFE) AF: 0.0000130 AC: 14 AN: 1077366

Other (OTH) AF: 0.00 AC: 0 AN: 57910

GnomAD4 genome AF: 0.000126 AC: 19 AN: 151274 Hom.: 0 Cov.: 0 AF XY: 0.0000949 AC XY: 7 AN XY: 73792

African (AFR) AF: 0.0000244 AC: 1 AN: 41002

American (AMR) AF: 0.00112 AC: 17 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3458

East Asian (EAS) AF: 0.00 AC: 0 AN: 5132

South Asian (SAS) AF: 0.00 AC: 0 AN: 4796

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10466

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67908

Other (OTH) AF: 0.000481 AC: 1 AN: 2080

Alfa AF: 0.000103 Hom.: 1042

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 03, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

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

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs368226832; hg19: chr6-50791584;