rs2817419

Positions:

• chr6-50845193-G-A
• chr6-50845193-G-T

Variant summary

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

The ENST00000393655.4(TFAP2B):​c.*1801G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.727 in 152,036 control chromosomes in the GnomAD database, including 40,121 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 0.73 (40120 hom., cov: 31)
  • Exomes 𝑓: 0.67 (1 hom.)
• Consequence: TFAP2B ENST00000393655.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.503

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.777 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TFAP2B	NM_003221.4	c.*1801G>A		3_prime_UTR_variant	7/7	ENST00000393655.4	NP_003212.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TFAP2B	ENST00000393655.4	c.*1801G>A		3_prime_UTR_variant	7/7	1	NM_003221.4	ENSP00000377265	P1

Frequencies

GnomAD3 genomes AF: 0.727 AC: 110375 AN: 151914 Hom.: 40084 Cov.: 31

Gnomad AFR AF: 0.696

Gnomad AMI AF: 0.761

Gnomad AMR AF: 0.756

Gnomad ASJ AF: 0.657

Gnomad EAS AF: 0.796

Gnomad SAS AF: 0.701

Gnomad FIN AF: 0.727

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.739

Gnomad OTH AF: 0.705

GnomAD4 exome AF: 0.667 AC: 4 AN: 6 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 FIN exome AF: 0.667

GnomAD4 genome AF: 0.727 AC: 110460 AN: 152030 Hom.: 40120 Cov.: 31 AF XY: 0.725 AC XY: 53900 AN XY: 74306

Gnomad4 AFR AF: 0.696

Gnomad4 AMR AF: 0.755

Gnomad4 ASJ AF: 0.657

Gnomad4 EAS AF: 0.797

Gnomad4 SAS AF: 0.701

Gnomad4 FIN AF: 0.727

Gnomad4 NFE AF: 0.739

Gnomad4 OTH AF: 0.709

Alfa AF: 0.727 Hom.: 30772

Bravo AF: 0.727

Asia WGS AF: 0.772 AC: 2685 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.3
DANN	Benign	0.76

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: rs2817419; hg19: chr6-50812906;