6-50830813-C-T

Variant names:

• chr6-50830813-C-T
• rs2206277
• NM_003221.4:c.601+2134C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003221.4(TFAP2B):​c.601+2134C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 152,068 control chromosomes in the GnomAD database, including 2,922 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 0.19 (2922 hom., cov: 32)
• Consequence: TFAP2B NM_003221.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31
• Publications: 51 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TFAP2B	NM_003221.4	c.601+2134C>T		intron_variant	Intron 3 of 6	ENST00000393655.4	NP_003212.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TFAP2B	ENST00000393655.4	c.601+2134C>T		intron_variant	Intron 3 of 6	1	NM_003221.4	ENSP00000377265.2

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28607 AN: 151948 Hom.: 2918 Cov.: 32

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.251

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.188 AC: 28632 AN: 152068 Hom.: 2922 Cov.: 32 AF XY: 0.190 AC XY: 14102 AN XY: 74346

African (AFR) AF: 0.143 AC: 5924 AN: 41488

American (AMR) AF: 0.285 AC: 4358 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 641 AN: 3470

East Asian (EAS) AF: 0.251 AC: 1297 AN: 5168

South Asian (SAS) AF: 0.225 AC: 1084 AN: 4808

European-Finnish (FIN) AF: 0.194 AC: 2055 AN: 10572

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.187 AC: 12692 AN: 67968

Other (OTH) AF: 0.199 AC: 420 AN: 2110

Alfa AF: 0.192 Hom.: 11314

Bravo AF: 0.195

Asia WGS AF: 0.278 AC: 967 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.080
DANN	Benign	0.25
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs2206277; hg19: chr6-50798526;