chr6-10411162-C-G

Variant names:

• chr6-10411162-C-G
• rs3798691
• NM_001372066.1:c.52-827G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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-AS1 (HGNC:40579): (TFAP2A antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFAP2A	NM_001372066.1	MANE Select	c.52-827G>C		intron	N/A	NP_001358995.1	A0A6E1XE14
	TFAP2A	NM_001042425.3		c.34-827G>C		intron	N/A	NP_001035890.1	P05549-6
	TFAP2A	NM_001032280.3		c.27+408G>C		intron	N/A	NP_001027451.1	P05549-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFAP2A	ENST00000379613.10	TSL:1 MANE Select	c.52-827G>C		intron	N/A	ENSP00000368933.5	A0A6E1XE14
	TFAP2A	ENST00000379608.9	TSL:1	c.27+408G>C		intron	N/A	ENSP00000368928.3	P05549-5
	TFAP2A	ENST00000466073.5	TSL:1	c.46-827G>C		intron	N/A	ENSP00000417495.1	C1K3N0

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

African (AFR) AF: 0.0239 AC: 45 AN: 1880

American (AMR) AF: 0.0853 AC: 334 AN: 3914

Ashkenazi Jewish (ASJ) AF: 0.0285 AC: 27 AN: 948

East Asian (EAS) AF: 0.220 AC: 578 AN: 2628

South Asian (SAS) AF: 0.0116 AC: 72 AN: 6214

European-Finnish (FIN) AF: 0.0314 AC: 38 AN: 1212

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 132

European-Non Finnish (NFE) AF: 0.0149 AC: 398 AN: 26696

Other (OTH) AF: 0.0254 AC: 56 AN: 2206

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

African (AFR) AF: 0.0312 AC: 1285 AN: 41232

American (AMR) AF: 0.0881 AC: 1337 AN: 15182

Ashkenazi Jewish (ASJ) AF: 0.0378 AC: 131 AN: 3470

East Asian (EAS) AF: 0.272 AC: 1388 AN: 5108

South Asian (SAS) AF: 0.0196 AC: 94 AN: 4798

European-Finnish (FIN) AF: 0.0398 AC: 415 AN: 10426

Middle Eastern (MID) AF: 0.0103 AC: 3 AN: 290

European-Non Finnish (NFE) AF: 0.0201 AC: 1368 AN: 67964

Other (OTH) AF: 0.0390 AC: 82 AN: 2102

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.019
DANN	Benign	0.67
PhyloP100		-2.6
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: rs3798691; hg19: chr6-10411395;