rs3798694

Variant names:

• chr6-10408524-C-T
• rs3798694
• NM_001372066.1:c.486+1377G>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.486+1377G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0783 in 152,270 control chromosomes in the GnomAD database, including 654 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 0.078 (654 hom., cov: 33)
• Consequence: TFAP2A NM_001372066.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.710
• 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: 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TFAP2A	NM_001372066.1	c.486+1377G>A		intron_variant	Intron 2 of 6	ENST00000379613.10	NP_001358995.1
TFAP2A	NM_001042425.3	c.468+1377G>A		intron_variant	Intron 2 of 6		NP_001035890.1
TFAP2A	NM_001032280.3	c.462+1377G>A		intron_variant	Intron 2 of 6		NP_001027451.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TFAP2A	ENST00000379613.10	c.486+1377G>A		intron_variant	Intron 2 of 6	1	NM_001372066.1	ENSP00000368933.5

Frequencies

GnomAD3 genomes AF: 0.0784 AC: 11923 AN: 152152 Hom.: 654 Cov.: 33

Gnomad AFR AF: 0.0210

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.0871

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.0348

Gnomad SAS AF: 0.0889

Gnomad FIN AF: 0.0744

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.0783 AC: 11921 AN: 152270 Hom.: 654 Cov.: 33 AF XY: 0.0778 AC XY: 5791 AN XY: 74468

African (AFR) AF: 0.0209 AC: 869 AN: 41570

American (AMR) AF: 0.0870 AC: 1330 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 669 AN: 3472

East Asian (EAS) AF: 0.0349 AC: 181 AN: 5184

South Asian (SAS) AF: 0.0889 AC: 429 AN: 4824

European-Finnish (FIN) AF: 0.0744 AC: 789 AN: 10604

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.107 AC: 7277 AN: 68016

Other (OTH) AF: 0.104 AC: 220 AN: 2110

Alfa AF: 0.0877 Hom.: 94

Bravo AF: 0.0763

Asia WGS AF: 0.0490 AC: 172 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.0
DANN	Benign	0.61
PhyloP100		0.71
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: rs3798694; hg19: chr6-10408757;