rs17635655

chr6-10418337-A-T

Variant summary

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

The NM_001042425.3(TFAP2A):c.33+1081T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 152,268 control chromosomes in the GnomAD database, including 3,314 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 0.18 (3314 hom., cov: 33)
  • Exomes 𝑓: 0.21 (0 hom.)
• Consequence: TFAP2A NM_001042425.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TFAP2A	NM_001042425.3	c.33+1081T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TFAP2A	ENST00000319516.8	c.33+1081T>A		intron_variant		5		A1
TFAP2A	ENST00000486038.1	n.554T>A		non_coding_transcript_exon_variant	2/2	5
TFAP2A	ENST00000464323.1	n.137+1081T>A		intron_variant, non_coding_transcript_variant		2
TFAP2A	ENST00000473652.1	n.242+1081T>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27160 AN: 152136 Hom.: 3308 Cov.: 33

Gnomad AFR AF: 0.0432

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.0610

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.162

GnomAD4 exome AF: 0.214 AC: 3 AN: 14 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 FIN exome AF: 0.333

Gnomad4 NFE exome AF: 0.125

GnomAD4 genome AF: 0.179 AC: 27182 AN: 152254 Hom.: 3314 Cov.: 33 AF XY: 0.181 AC XY: 13486 AN XY: 74442

Gnomad4 AFR AF: 0.0430

Gnomad4 AMR AF: 0.269

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.0613

Gnomad4 SAS AF: 0.200

Gnomad4 FIN AF: 0.311

Gnomad4 NFE AF: 0.230

Gnomad4 OTH AF: 0.161

Alfa AF: 0.207 Hom.: 448

Bravo AF: 0.170

Asia WGS AF: 0.141 AC: 492 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
Cadd	Benign	15
Dann	Benign	0.90

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17635655; hg19: chr6-10418570;