chr6-10411955-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 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=-0.58).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001032280.3. 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.52-1620A>G		intron	N/A	NP_001358995.1
	TFAP2A	NM_001032280.3		c.-359A>G		5_prime_UTR	Exon 1 of 7	NP_001027451.1
	TFAP2A	NM_001042425.3		c.34-1620A>G		intron	N/A	NP_001035890.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFAP2A	ENST00000379608.9	TSL:1	c.-359A>G		5_prime_UTR	Exon 1 of 7	ENSP00000368928.3
	TFAP2A	ENST00000379613.10	TSL:1 MANE Select	c.52-1620A>G		intron	N/A	ENSP00000368933.5
	TFAP2A	ENST00000466073.5	TSL:1	c.46-1620A>G		intron	N/A	ENSP00000417495.1

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

African (AFR) AF: 0.109 AC: 2028 AN: 18526

American (AMR) AF: 0.482 AC: 3065 AN: 6364

Ashkenazi Jewish (ASJ) AF: 0.398 AC: 3204 AN: 8054

East Asian (EAS) AF: 0.155 AC: 1536 AN: 9892

South Asian (SAS) AF: 0.483 AC: 14802 AN: 30620

European-Finnish (FIN) AF: 0.522 AC: 2678 AN: 5128

Middle Eastern (MID) AF: 0.360 AC: 743 AN: 2066

European-Non Finnish (NFE) AF: 0.455 AC: 379025 AN: 833188

Other (OTH) AF: 0.418 AC: 14071 AN: 33636

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

African (AFR) AF: 0.137 AC: 5672 AN: 41528

American (AMR) AF: 0.444 AC: 6798 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 1351 AN: 3468

East Asian (EAS) AF: 0.162 AC: 833 AN: 5154

South Asian (SAS) AF: 0.474 AC: 2288 AN: 4826

European-Finnish (FIN) AF: 0.546 AC: 5777 AN: 10590

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.461 AC: 31322 AN: 67986

Other (OTH) AF: 0.361 AC: 762 AN: 2112

Alfa AF: 0.426 Hom.: 24400

Bravo AF: 0.343

Asia WGS AF: 0.344 AC: 1200 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	18
DANN	Benign	0.78
PhyloP100		0.87
PromoterAI		0.024	Neutral
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: rs1675414; hg19: chr6-10412188; COSMIC: COSV60235442; COSMIC: COSV60235442;