chr6-50818295-T-A

Variant names:

• chr6-50818295-T-A
• rs2206271
• ENST00000745639.1:n.343+607A>T

Variant summary

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

The ENST00000745639.1(ENSG00000297125):​n.343+607A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 151,728 control chromosomes in the GnomAD database, including 8,083 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 0.32 (8083 hom., cov: 32)
• Consequence: ENSG00000297125 ENST00000745639.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28
• Publications: 15 publications found

Genes affected

ENSG00000297125 (HGNC:):

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: PanelApp Australia, G2P, Orphanet, Labcorp Genetics (formerly Invitae)
• TFAP2B-related congenital heart disease spectrum disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• patent ductus arteriosus 2

  Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia
• 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=-0.53).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000745639.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000297125	ENST00000745639.1		n.343+607A>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.324 AC: 49048 AN: 151608 Hom.: 8066 Cov.: 32

Gnomad AFR AF: 0.334

Gnomad AMI AF: 0.210

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.363

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.290

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.329

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

GnomAD4 genome AF: 0.324 AC: 49102 AN: 151728 Hom.: 8083 Cov.: 32 AF XY: 0.324 AC XY: 24004 AN XY: 74148

African (AFR) AF: 0.334 AC: 13803 AN: 41374

American (AMR) AF: 0.386 AC: 5878 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 983 AN: 3472

East Asian (EAS) AF: 0.363 AC: 1876 AN: 5164

South Asian (SAS) AF: 0.348 AC: 1668 AN: 4794

European-Finnish (FIN) AF: 0.332 AC: 3476 AN: 10482

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.301 AC: 20437 AN: 67882

Other (OTH) AF: 0.333 AC: 703 AN: 2110

Alfa AF: 0.331 Hom.: 1065

Bravo AF: 0.329

Asia WGS AF: 0.429 AC: 1490 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	14
DANN	Benign	0.82
PhyloP100		1.3
PromoterAI		0.0022	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2206271;

hg19: chr6-50786008;