rs533558

chr6-10395339-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The XR_007059911.1(LOC124901485):n.1013+317T>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.481 in 152,058 control chromosomes in the GnomAD database, including 19,543 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 0.48 (19543 hom., cov: 32)
• Consequence: LOC124901485 XR_007059911.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07

Genes affected

LOC124901485 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC124901485	XR_007059911.1	n.1013+317T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TFAP2A	ENST00000461628.5	c.207-1778T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.481 AC: 73111 AN: 151940 Hom.: 19497 Cov.: 32

Gnomad AFR AF: 0.712

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.506

Gnomad EAS AF: 0.319

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.458

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.466

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

GnomAD4 genome AF: 0.481 AC: 73206 AN: 152058 Hom.: 19543 Cov.: 32 AF XY: 0.481 AC XY: 35743 AN XY: 74326

Gnomad4 AFR AF: 0.712

Gnomad4 AMR AF: 0.451

Gnomad4 ASJ AF: 0.506

Gnomad4 EAS AF: 0.320

Gnomad4 SAS AF: 0.330

Gnomad4 FIN AF: 0.458

Gnomad4 NFE AF: 0.377

Gnomad4 OTH AF: 0.460

Alfa AF: 0.397 Hom.: 21233

Bravo AF: 0.495

Asia WGS AF: 0.300 AC: 1044 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
Cadd	Benign	16
Dann	Benign	0.79

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs533558; hg19: chr6-10395572;