dbSNP rs2857513: TFAP2B:c.*10A>T (chr6-50843402-A-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.823

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
TFAP2B	NM_003221.4 link	c.*10A>T		3_prime_UTR_variant	Exon 7 of 7	ENST00000393655.4	NP_003212.2	Q92481-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TFAP2B	ENST00000393655.4 link	c.*10A>T		3_prime_UTR_variant	Exon 7 of 7	1	NM_003221.4	ENSP00000377265.2		Q92481-1

Frequencies

GnomAD3 genomes

AF:

0.140

AC:

21249

AN:

152064

Hom.:

1597

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.115

AC XY:

83345

AN XY:

725116

show subpopulations

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.:

AF XY:

0.140

AC XY:

10394

AN XY:

74422

show subpopulations

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

LINK: link

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over