6-10394973-C-T

Variant names:

• chr6-10394973-C-T
• rs537112
• ENST00000461628.5:c.206-1412G>A

Variant summary

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

The ENST00000461628.5(TFAP2A):​c.206-1412G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 151,886 control chromosomes in the GnomAD database, including 2,966 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 0.16 (2966 hom., cov: 32)
• Consequence: TFAP2A ENST00000461628.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0360
• Publications: 2 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: Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P, Orphanet

LOC124901485 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.319 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFAP2A	ENST00000461628.5	TSL:3	c.206-1412G>A		intron	N/A	ENSP00000417735.1	H7C4N4

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24445 AN: 151768 Hom.: 2961 Cov.: 32

Gnomad AFR AF: 0.324

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.0753

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.0297

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0732

Gnomad OTH AF: 0.146

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

GnomAD4 genome AF: 0.161 AC: 24493 AN: 151886 Hom.: 2966 Cov.: 32 AF XY: 0.163 AC XY: 12109 AN XY: 74226

African (AFR) AF: 0.324 AC: 13401 AN: 41388

American (AMR) AF: 0.145 AC: 2218 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0753 AC: 261 AN: 3468

East Asian (EAS) AF: 0.276 AC: 1427 AN: 5164

South Asian (SAS) AF: 0.0297 AC: 142 AN: 4784

European-Finnish (FIN) AF: 0.160 AC: 1681 AN: 10528

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0732 AC: 4972 AN: 67968

Other (OTH) AF: 0.143 AC: 302 AN: 2114

Alfa AF: 0.0910 Hom.: 1385

Bravo AF: 0.173

Asia WGS AF: 0.126 AC: 438 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.0
DANN	Benign	0.61
PhyloP100		0.036

Splicing

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

Other links and lift over

dbSNP: rs537112; hg19: chr6-10395206;