rs533558

Variant names:

• chr6-10395339-A-G
• rs533558
• ENST00000461628.5:c.206-1778T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000461628.5(TFAP2A):​c.206-1778T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.481 in 152,058 control chromosomes in the GnomAD database, including 19,543 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 0.48 (19543 hom., cov: 32)
• Consequence: TFAP2A ENST00000461628.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07
• Publications: 8 publications found

Genes affected

TFAP2A (HGNC:11742): (transcription factor AP-2 alpha) The protein encoded by this gene is a transcription factor that binds the consensus sequence 5'-GCCNNNGGC-3'. The encoded protein functions as either a homodimer or as a heterodimer with similar family members. This protein activates the transcription of some genes while inhibiting the transcription of others. Defects in this gene are a cause of branchiooculofacial syndrome (BOFS). Three transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Dec 2009]

TFAP2A Gene-Disease associations (from GenCC):

• branchiooculofacial syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)

LOC124901485 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000461628.5. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFAP2A	ENST00000461628.5	TSL:3	c.206-1778T>C		intron	N/A	ENSP00000417735.1

Frequencies

GnomAD3 genomes AF: 0.481 AC: 73111 AN: 151940 Hom.: 19497 Cov.: 32

Gnomad AFR AF: 0.712

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.506

Gnomad EAS AF: 0.319

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.458

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.466

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

GnomAD4 genome AF: 0.481 AC: 73206 AN: 152058 Hom.: 19543 Cov.: 32 AF XY: 0.481 AC XY: 35743 AN XY: 74326

African (AFR) AF: 0.712 AC: 29522 AN: 41458

American (AMR) AF: 0.451 AC: 6900 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.506 AC: 1756 AN: 3472

East Asian (EAS) AF: 0.320 AC: 1651 AN: 5164

South Asian (SAS) AF: 0.330 AC: 1591 AN: 4818

European-Finnish (FIN) AF: 0.458 AC: 4829 AN: 10554

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.377 AC: 25608 AN: 67988

Other (OTH) AF: 0.460 AC: 970 AN: 2110

Alfa AF: 0.419 Hom.: 42579

Bravo AF: 0.495

Asia WGS AF: 0.300 AC: 1044 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	16
DANN	Benign	0.79
PhyloP100		1.1

Splicing

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

Other links and lift over

dbSNP: rs533558; hg19: chr6-10395572;