chr6-50823769-C-T

Variant names:

• chr6-50823769-C-T
• rs13216733
• NM_003221.4:c.444C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The ENST00000393655.4(TFAP2B):​c.444C>T​(p.Asp148Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,446,118 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: TFAP2B ENST00000393655.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.177
• 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP7: Synonymous conserved (PhyloP=0.177 with no splicing effect.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFAP2B	NM_003221.4	MANE Select	c.444C>T	p.Asp148Asp	synonymous	Exon 2 of 7	NP_003212.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFAP2B	ENST00000393655.4	TSL:1 MANE Select	c.444C>T	p.Asp148Asp	synonymous	Exon 2 of 7	ENSP00000377265.2
	TFAP2B	ENST00000344788.7	TSL:3	c.438C>T	p.Asp146Asp	synonymous	Exon 3 of 4	ENSP00000342252.3
	TFAP2B	ENST00000489228.1	TSL:2	n.739C>T		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000142 AC: 3 AN: 210786 AF XY: 0.00

Gnomad AFR exome AF: 0.000170

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000110

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000207 AC: 3 AN: 1446118 Hom.: 0 Cov.: 34 AF XY: 0.00000139 AC XY: 1 AN XY: 717912

African (AFR) AF: 0.00 AC: 0 AN: 33138

American (AMR) AF: 0.00 AC: 0 AN: 42464

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25794

East Asian (EAS) AF: 0.0000257 AC: 1 AN: 38938

South Asian (SAS) AF: 0.00 AC: 0 AN: 84202

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51722

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 9.05e-7 AC: 1 AN: 1104370

Other (OTH) AF: 0.0000167 AC: 1 AN: 59740

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	13
DANN	Benign	0.87
PhyloP100		0.18

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

Other links and lift over

dbSNP: rs13216733; hg19: chr6-50791482;