rs2857513

Positions:

• chr6-50843402-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003221.4(TFAP2B):​c.*10A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 1,610,240 control chromosomes in the GnomAD database, including 11,571 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1603 hom., cov: 33)
  • Exomes 𝑓: 0.12 (9968 hom.)
• Consequence: TFAP2B NM_003221.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.823

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 6-50843402-A-T is Benign according to our data. Variant chr6-50843402-A-T is described in ClinVar as [Benign]. Clinvar id is 258983.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TFAP2B	NM_003221.4	c.*10A>T		3_prime_UTR_variant	7/7	ENST00000393655.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TFAP2B	ENST00000393655.4	c.*10A>T		3_prime_UTR_variant	7/7	1	NM_003221.4	P1

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21249 AN: 152064 Hom.: 1597 Cov.: 33

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.0962

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.132

GnomAD3 exomes AF: 0.118 AC: 28657 AN: 242878 Hom.: 1815 AF XY: 0.117 AC XY: 15539 AN XY: 132628

Gnomad AFR exome AF: 0.205

Gnomad AMR exome AF: 0.0702

Gnomad ASJ exome AF: 0.106

Gnomad EAS exome AF: 0.129

Gnomad SAS exome AF: 0.118

Gnomad FIN exome AF: 0.153

Gnomad NFE exome AF: 0.114

Gnomad OTH exome AF: 0.108

GnomAD4 exome AF: 0.115 AC: 167946 AN: 1458058 Hom.: 9968 Cov.: 32 AF XY: 0.115 AC XY: 83345 AN XY: 725116

Gnomad4 AFR exome AF: 0.205

Gnomad4 AMR exome AF: 0.0731

Gnomad4 ASJ exome AF: 0.102

Gnomad4 EAS exome AF: 0.101

Gnomad4 SAS exome AF: 0.114

Gnomad4 FIN exome AF: 0.154

Gnomad4 NFE exome AF: 0.113

Gnomad4 OTH exome AF: 0.117

GnomAD4 genome AF: 0.140 AC: 21285 AN: 152182 Hom.: 1603 Cov.: 33 AF XY: 0.140 AC XY: 10394 AN XY: 74422

Gnomad4 AFR AF: 0.198

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.0962

Gnomad4 EAS AF: 0.125

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.159

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.138

Alfa AF: 0.129 Hom.: 162

Bravo AF: 0.137

Asia WGS AF: 0.154 AC: 532 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.36
DANN	Benign	0.72

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: rs2857513; hg19: chr6-50811115;