rs2857513

Variant names:

• chr6-50843402-A-T
• rs2857513
• NM_003221.4:c.*10A>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 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 -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 VariationId 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 rank	MANE	Protein	UniProt
TFAP2B	NM_003221.4	c.*10A>T		3_prime_UTR_variant	Exon 7 of 7	ENST00000393655.4	NP_003212.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TFAP2B	ENST00000393655.4	c.*10A>T		3_prime_UTR_variant	Exon 7 of 7	1	NM_003221.4	ENSP00000377265.2

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

GnomAD2 exomes AF: 0.118 AC: 28657 AN: 242878 AF XY: 0.117

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 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

African (AFR) AF: 0.205 AC: 6804 AN: 33166

American (AMR) AF: 0.0731 AC: 3239 AN: 44292

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 2663 AN: 26068

East Asian (EAS) AF: 0.101 AC: 3987 AN: 39588

South Asian (SAS) AF: 0.114 AC: 9717 AN: 85116

European-Finnish (FIN) AF: 0.154 AC: 8184 AN: 53214

Middle Eastern (MID) AF: 0.121 AC: 696 AN: 5754

European-Non Finnish (NFE) AF: 0.113 AC: 125616 AN: 1110632

Other (OTH) AF: 0.117 AC: 7040 AN: 60228

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

African (AFR) AF: 0.198 AC: 8199 AN: 41488

American (AMR) AF: 0.103 AC: 1572 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0962 AC: 334 AN: 3472

East Asian (EAS) AF: 0.125 AC: 650 AN: 5180

South Asian (SAS) AF: 0.122 AC: 587 AN: 4822

European-Finnish (FIN) AF: 0.159 AC: 1682 AN: 10600

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.115 AC: 7853 AN: 67998

Other (OTH) AF: 0.138 AC: 291 AN: 2116

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

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

May 05, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.36
DANN	Benign	0.72
PhyloP100		-0.82
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: rs2857513; hg19: chr6-50811115;