6-50845193-G-A

Variant names:

• chr6-50845193-G-A
• rs2817419
• NM_003221.4:c.*1801G>A

Variant summary

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

The NM_003221.4(TFAP2B):​c.*1801G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.727 in 152,036 control chromosomes in the GnomAD database, including 40,121 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 0.73 (40120 hom., cov: 31)
  • Exomes 𝑓: 0.67 (1 hom.)
• Consequence: TFAP2B NM_003221.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.503
• Publications: 19 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.777 is higher than 0.05.

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.*1801G>A		3_prime_UTR	Exon 7 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.*1801G>A		3_prime_UTR	Exon 7 of 7	ENSP00000377265.2

Frequencies

GnomAD3 genomes AF: 0.727 AC: 110375 AN: 151914 Hom.: 40084 Cov.: 31

Gnomad AFR AF: 0.696

Gnomad AMI AF: 0.761

Gnomad AMR AF: 0.756

Gnomad ASJ AF: 0.657

Gnomad EAS AF: 0.796

Gnomad SAS AF: 0.701

Gnomad FIN AF: 0.727

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.739

Gnomad OTH AF: 0.705

GnomAD4 exome AF: 0.667 AC: 4 AN: 6 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.667 AC: 4 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.727 AC: 110460 AN: 152030 Hom.: 40120 Cov.: 31 AF XY: 0.725 AC XY: 53900 AN XY: 74306

African (AFR) AF: 0.696 AC: 28833 AN: 41428

American (AMR) AF: 0.755 AC: 11553 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.657 AC: 2278 AN: 3466

East Asian (EAS) AF: 0.797 AC: 4107 AN: 5154

South Asian (SAS) AF: 0.701 AC: 3382 AN: 4822

European-Finnish (FIN) AF: 0.727 AC: 7677 AN: 10566

Middle Eastern (MID) AF: 0.658 AC: 192 AN: 292

European-Non Finnish (NFE) AF: 0.739 AC: 50249 AN: 67984

Other (OTH) AF: 0.709 AC: 1495 AN: 2110

Alfa AF: 0.729 Hom.: 45729

Bravo AF: 0.727

Asia WGS AF: 0.772 AC: 2685 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.3
DANN	Benign	0.76
PhyloP100		0.50
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: rs2817419; hg19: chr6-50812906;