6-10403417-C-T

Variant names:

• chr6-10403417-C-T
• rs3798696
• NM_001372066.1:c.771-807G>A

Variant summary

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

The NM_001372066.1(TFAP2A):​c.771-807G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,136 control chromosomes in the GnomAD database, including 892 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 0.10 (892 hom., cov: 33)
• Consequence: TFAP2A NM_001372066.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.468
• 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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001372066.1. 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
	TFAP2A	NM_001372066.1	MANE Select	c.771-807G>A		intron	N/A	NP_001358995.1
	TFAP2A	NM_001042425.3		c.753-807G>A		intron	N/A	NP_001035890.1
	TFAP2A	NM_001032280.3		c.747-807G>A		intron	N/A	NP_001027451.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFAP2A	ENST00000379613.10	TSL:1 MANE Select	c.771-807G>A		intron	N/A	ENSP00000368933.5
	TFAP2A	ENST00000379608.9	TSL:1	c.747-807G>A		intron	N/A	ENSP00000368928.3
	TFAP2A	ENST00000466073.5	TSL:1	c.765-807G>A		intron	N/A	ENSP00000417495.1

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15571 AN: 152018 Hom.: 893 Cov.: 33

Gnomad AFR AF: 0.0865

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.0994

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.0369

Gnomad SAS AF: 0.0963

Gnomad FIN AF: 0.0827

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.124

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

GnomAD4 genome AF: 0.102 AC: 15564 AN: 152136 Hom.: 892 Cov.: 33 AF XY: 0.101 AC XY: 7479 AN XY: 74380

African (AFR) AF: 0.0861 AC: 3574 AN: 41486

American (AMR) AF: 0.0992 AC: 1517 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 684 AN: 3470

East Asian (EAS) AF: 0.0370 AC: 192 AN: 5194

South Asian (SAS) AF: 0.0963 AC: 464 AN: 4816

European-Finnish (FIN) AF: 0.0827 AC: 875 AN: 10586

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.115 AC: 7839 AN: 67980

Other (OTH) AF: 0.123 AC: 259 AN: 2108

Alfa AF: 0.118 Hom.: 1924

Bravo AF: 0.103

Asia WGS AF: 0.0600 AC: 209 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	10
DANN	Benign	0.73
PhyloP100		-0.47
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: rs3798696; hg19: chr6-10403650;