rs3798691

chr6-10411162-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001372066.1(TFAP2A):c.52-827G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0388 in 197,312 control chromosomes in the GnomAD database, including 413 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 0.040 (316 hom., cov: 30)
  • Exomes 𝑓: 0.034 (97 hom.)
• Consequence: TFAP2A NM_001372066.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.60

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-AS1 (HGNC:40579): (TFAP2A antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TFAP2A	NM_001372066.1	c.52-827G>C		intron_variant		ENST00000379613.10
TFAP2A	NM_001032280.3	c.27+408G>C		intron_variant
TFAP2A	NM_001042425.3	c.34-827G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TFAP2A	ENST00000379613.10	c.52-827G>C		intron_variant		1	NM_001372066.1	A1
TFAP2A-AS1	ENST00000420777.1	n.58+1765C>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0403 AC: 6107 AN: 151368 Hom.: 317 Cov.: 30

Gnomad AFR AF: 0.0312

Gnomad AMI AF: 0.00989

Gnomad AMR AF: 0.0877

Gnomad ASJ AF: 0.0378

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.0196

Gnomad FIN AF: 0.0398

Gnomad MID AF: 0.00962

Gnomad NFE AF: 0.0201

Gnomad OTH AF: 0.0404

GnomAD4 exome AF: 0.0338 AC: 1548 AN: 45830 Hom.: 97 AF XY: 0.0344 AC XY: 848 AN XY: 24656

Gnomad4 AFR exome AF: 0.0239

Gnomad4 AMR exome AF: 0.0853

Gnomad4 ASJ exome AF: 0.0285

Gnomad4 EAS exome AF: 0.220

Gnomad4 SAS exome AF: 0.0116

Gnomad4 FIN exome AF: 0.0314

Gnomad4 NFE exome AF: 0.0149

Gnomad4 OTH exome AF: 0.0254

GnomAD4 genome AF: 0.0403 AC: 6112 AN: 151482 Hom.: 316 Cov.: 30 AF XY: 0.0428 AC XY: 3168 AN XY: 73976

Gnomad4 AFR AF: 0.0312

Gnomad4 AMR AF: 0.0881

Gnomad4 ASJ AF: 0.0378

Gnomad4 EAS AF: 0.272

Gnomad4 SAS AF: 0.0196

Gnomad4 FIN AF: 0.0398

Gnomad4 NFE AF: 0.0201

Gnomad4 OTH AF: 0.0390

Alfa AF: 0.0311 Hom.: 15

Bravo AF: 0.0471

Asia WGS AF: 0.101 AC: 350 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.019
Dann	Benign	0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs3798691; hg19: chr6-10411395;