6-10411955-T-C

Variant names:

• chr6-10411955-T-C
• rs1675414
• ENST00000379608.9:c.-359A>G

Variant summary

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

The NM_001032280.3(TFAP2A):​c.-359A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 1,099,642 control chromosomes in the GnomAD database, including 107,729 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 0.36 (11958 hom., cov: 33)
  • Exomes 𝑓: 0.44 (95771 hom.)
• Consequence: TFAP2A NM_001032280.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.866

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TFAP2A	NM_001372066.1	c.52-1620A>G		intron_variant	Intron 1 of 6	ENST00000379613.10	NP_001358995.1
TFAP2A	NM_001032280.3	c.-359A>G		5_prime_UTR_variant	Exon 1 of 7		NP_001027451.1
TFAP2A	NM_001042425.3	c.34-1620A>G		intron_variant	Intron 1 of 6		NP_001035890.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TFAP2A	ENST00000379613.10	c.52-1620A>G		intron_variant	Intron 1 of 6	1	NM_001372066.1	ENSP00000368933.5

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55320 AN: 152048 Hom.: 11950 Cov.: 33

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.473

Gnomad FIN AF: 0.546

Gnomad MID AF: 0.331

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.363

GnomAD4 exome AF: 0.445 AC: 421152 AN: 947474 Hom.: 95771 Cov.: 32 AF XY: 0.446 AC XY: 198362 AN XY: 445102

Gnomad4 AFR exome AF: 0.109

Gnomad4 AMR exome AF: 0.482

Gnomad4 ASJ exome AF: 0.398

Gnomad4 EAS exome AF: 0.155

Gnomad4 SAS exome AF: 0.483

Gnomad4 FIN exome AF: 0.522

Gnomad4 NFE exome AF: 0.455

Gnomad4 OTH exome AF: 0.418

GnomAD4 genome AF: 0.364 AC: 55332 AN: 152168 Hom.: 11958 Cov.: 33 AF XY: 0.367 AC XY: 27316 AN XY: 74398

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.444

Gnomad4 ASJ AF: 0.390

Gnomad4 EAS AF: 0.162

Gnomad4 SAS AF: 0.474

Gnomad4 FIN AF: 0.546

Gnomad4 NFE AF: 0.461

Gnomad4 OTH AF: 0.361

Alfa AF: 0.435 Hom.: 19983

Bravo AF: 0.343

Asia WGS AF: 0.344 AC: 1200 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	18
DANN	Benign	0.78

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

Publications

LitVar

Other links and lift over

dbSNP: rs1675414; hg19: chr6-10412188; COSMIC: COSV60235442; COSMIC: COSV60235442;