rs6930924

Variant names:

• chr6-50822920-G-A
• rs6930924
• NM_003221.4:c.82-487G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-50822920-G-A
• chr6-50822920-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003221.4(TFAP2B):​c.82-487G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 152,054 control chromosomes in the GnomAD database, including 2,854 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 (2854 hom., cov: 32)
• Consequence: TFAP2B NM_003221.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.115
• Publications: 9 publications found

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]

TFAP2B Gene-Disease associations (from GenCC):

• Char syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet
• familial patent arterial duct

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TFAP2B	NM_003221.4	c.82-487G>A		intron_variant	Intron 1 of 6	ENST00000393655.4	NP_003212.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TFAP2B	ENST00000393655.4	c.82-487G>A		intron_variant	Intron 1 of 6	1	NM_003221.4	ENSP00000377265.2
TFAP2B	ENST00000344788.7	c.76-487G>A		intron_variant	Intron 2 of 3	3		ENSP00000342252.3
TFAP2B	ENST00000489228.1	n.377-487G>A		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26432 AN: 151938 Hom.: 2851 Cov.: 32

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.0659

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.170

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

GnomAD4 genome AF: 0.174 AC: 26446 AN: 152054 Hom.: 2854 Cov.: 32 AF XY: 0.180 AC XY: 13365 AN XY: 74304

African (AFR) AF: 0.294 AC: 12170 AN: 41448

American (AMR) AF: 0.146 AC: 2234 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 610 AN: 3472

East Asian (EAS) AF: 0.206 AC: 1062 AN: 5160

South Asian (SAS) AF: 0.188 AC: 908 AN: 4818

European-Finnish (FIN) AF: 0.193 AC: 2039 AN: 10562

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.102 AC: 6960 AN: 67996

Other (OTH) AF: 0.168 AC: 356 AN: 2114

Alfa AF: 0.102 Hom.: 475

Bravo AF: 0.176

Asia WGS AF: 0.180 AC: 625 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.83
DANN	Benign	0.47
PhyloP100		-0.12
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: rs6930924; hg19: chr6-50790633;