6-50821738-T-C

Variant names:

• chr6-50821738-T-C
• rs2076309
• NM_003221.4:c.82-1669T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_003221.4(TFAP2B):​c.82-1669T>C variant causes a intron change. The variant allele was found at a frequency of 0.607 in 171,014 control chromosomes in the GnomAD database, including 32,179 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 0.61 (28983 hom., cov: 31)
  • Exomes 𝑓: 0.56 (3196 hom.)
• Consequence: TFAP2B NM_003221.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.78
• Publications: 2 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: Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia, G2P
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.711 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003221.4. 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
	TFAP2B	NM_003221.4	MANE Select	c.82-1669T>C		intron	N/A	NP_003212.2	Q92481-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFAP2B	ENST00000393655.4	TSL:1 MANE Select	c.82-1669T>C		intron	N/A	ENSP00000377265.2	Q92481-1
	TFAP2B	ENST00000344788.7	TSL:3	c.49-396T>C		intron	N/A	ENSP00000342252.3	X6R4Y8
	TFAP2B	ENST00000489228.1	TSL:2	n.-47T>C		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.613 AC: 93005 AN: 151774 Hom.: 28956 Cov.: 31

Gnomad AFR AF: 0.718

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.636

Gnomad ASJ AF: 0.622

Gnomad EAS AF: 0.571

Gnomad SAS AF: 0.637

Gnomad FIN AF: 0.602

Gnomad MID AF: 0.631

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.634

GnomAD4 exome AF: 0.560 AC: 10708 AN: 19122 Hom.: 3196 Cov.: 0 AF XY: 0.564 AC XY: 5736 AN XY: 10162

African (AFR) AF: 0.717 AC: 363 AN: 506

American (AMR) AF: 0.655 AC: 1408 AN: 2150

Ashkenazi Jewish (ASJ) AF: 0.602 AC: 225 AN: 374

East Asian (EAS) AF: 0.579 AC: 785 AN: 1356

South Asian (SAS) AF: 0.606 AC: 1391 AN: 2296

European-Finnish (FIN) AF: 0.557 AC: 364 AN: 654

Middle Eastern (MID) AF: 0.583 AC: 21 AN: 36

European-Non Finnish (NFE) AF: 0.523 AC: 5711 AN: 10924

Other (OTH) AF: 0.533 AC: 440 AN: 826

GnomAD4 genome AF: 0.613 AC: 93088 AN: 151892 Hom.: 28983 Cov.: 31 AF XY: 0.615 AC XY: 45644 AN XY: 74250

African (AFR) AF: 0.718 AC: 29709 AN: 41380

American (AMR) AF: 0.637 AC: 9719 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.622 AC: 2156 AN: 3468

East Asian (EAS) AF: 0.571 AC: 2945 AN: 5160

South Asian (SAS) AF: 0.637 AC: 3067 AN: 4816

European-Finnish (FIN) AF: 0.602 AC: 6347 AN: 10538

Middle Eastern (MID) AF: 0.640 AC: 187 AN: 292

European-Non Finnish (NFE) AF: 0.548 AC: 37217 AN: 67958

Other (OTH) AF: 0.635 AC: 1334 AN: 2102

Alfa AF: 0.555 Hom.: 7619

Bravo AF: 0.621

Asia WGS AF: 0.655 AC: 2277 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	20
DANN	Benign	0.81
PhyloP100		3.8
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: rs2076309; hg19: chr6-50789451;