rs987237

chr6-50835337-A-G

Variant summary

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

The NM_003221.4(TFAP2B):c.602-724A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 152,228 control chromosomes in the GnomAD database, including 2,544 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 0.17 (2544 hom., cov: 33)
• Consequence: TFAP2B NM_003221.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12

Genes affected

TFAP2B (HGNC:11743): (transcription factor AP-2 beta) This gene encodes a member of the AP-2 family of transcription factors. AP-2 proteins form homo- or hetero-dimers with other AP-2 family members and bind specific DNA sequences. They are thought to stimulate cell proliferation and suppress terminal differentiation of specific cell types during embryonic development. Specific AP-2 family members differ in their expression patterns and binding affinity for different promoters. This protein functions as both a transcriptional activator and repressor. Mutations in this gene result in autosomal dominant Char syndrome, suggesting that this gene functions in the differentiation of neural crest cell derivatives. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TFAP2B	NM_003221.4	c.602-724A>G		intron_variant		ENST00000393655.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TFAP2B	ENST00000393655.4	c.602-724A>G		intron_variant		1	NM_003221.4	P1

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26228 AN: 152112 Hom.: 2544 Cov.: 33

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.189

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

GnomAD4 genome AF: 0.172 AC: 26236 AN: 152228 Hom.: 2544 Cov.: 33 AF XY: 0.174 AC XY: 12967 AN XY: 74422

Gnomad4 AFR AF: 0.102

Gnomad4 AMR AF: 0.280

Gnomad4 ASJ AF: 0.156

Gnomad4 EAS AF: 0.164

Gnomad4 SAS AF: 0.218

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.188

Alfa AF: 0.187 Hom.: 6259

Bravo AF: 0.178

Asia WGS AF: 0.228 AC: 793 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
Cadd	Benign	18
Dann	Benign	0.74

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: rs987237; hg19: chr6-50803050;