rs2272903

Variant names:

• chr6-50818858-G-A
• rs2272903
• XM_017011233.2:c.59G>A
• TFAP2B p.Ser20Asn

Your query was ambiguous. Multiple possible variants found:

• chr6-50818858-G-A
• chr6-50818858-G-C

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The ENST00000344788.7(TFAP2B):​c.-67G>A variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.126 in 1,600,400 control chromosomes in the GnomAD database, including 15,106 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2795 hom., cov: 32)
  • Exomes 𝑓: 0.12 (12311 hom.)
• Consequence: TFAP2B ENST00000344788.7 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 6.23
• Publications: 21 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: 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

ENSG00000297125 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 6-50818858-G-A is Benign according to our data. Variant chr6-50818858-G-A is described in ClinVar as Benign. ClinVar VariationId is 1273651.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000344788.7. 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.-34G>A		upstream_gene	N/A	NP_003212.2	Q92481-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFAP2B	ENST00000344788.7	TSL:3	c.-67G>A		5_prime_UTR	Exon 1 of 4	ENSP00000342252.3	X6R4Y8
	ENSG00000297125	ENST00000745639.1		n.343+44C>T		intron	N/A
	TFAP2B	ENST00000393655.4	TSL:1 MANE Select	c.-34G>A		upstream_gene	N/A	ENSP00000377265.2	Q92481-1

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26273 AN: 151822 Hom.: 2792 Cov.: 32

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.0681

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.169

GnomAD2 exomes AF: 0.149 AC: 37476 AN: 250704 AF XY: 0.149

Gnomad AFR exome AF: 0.295

Gnomad AMR exome AF: 0.118

Gnomad ASJ exome AF: 0.171

Gnomad EAS exome AF: 0.228

Gnomad FIN exome AF: 0.187

Gnomad NFE exome AF: 0.105

Gnomad OTH exome AF: 0.154

GnomAD4 exome AF: 0.122 AC: 176025 AN: 1448460 Hom.: 12311 Cov.: 28 AF XY: 0.123 AC XY: 88848 AN XY: 721588

African (AFR) AF: 0.299 AC: 9910 AN: 33184

American (AMR) AF: 0.121 AC: 5423 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 4345 AN: 26054

East Asian (EAS) AF: 0.226 AC: 8936 AN: 39618

South Asian (SAS) AF: 0.189 AC: 16276 AN: 85952

European-Finnish (FIN) AF: 0.175 AC: 9327 AN: 53158

Middle Eastern (MID) AF: 0.163 AC: 937 AN: 5740

European-Non Finnish (NFE) AF: 0.102 AC: 112690 AN: 1100116

Other (OTH) AF: 0.136 AC: 8181 AN: 59948

GnomAD4 genome AF: 0.173 AC: 26288 AN: 151940 Hom.: 2795 Cov.: 32 AF XY: 0.179 AC XY: 13294 AN XY: 74268

African (AFR) AF: 0.290 AC: 12013 AN: 41382

American (AMR) AF: 0.146 AC: 2230 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 611 AN: 3470

East Asian (EAS) AF: 0.207 AC: 1068 AN: 5154

South Asian (SAS) AF: 0.192 AC: 920 AN: 4802

European-Finnish (FIN) AF: 0.192 AC: 2028 AN: 10558

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.102 AC: 6955 AN: 67978

Other (OTH) AF: 0.168 AC: 354 AN: 2108

Alfa AF: 0.132 Hom.: 3401

Bravo AF: 0.175

Asia WGS AF: 0.182 AC: 632 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Char syndrome (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	21
DANN	Benign	0.93
PhyloP100		6.2
PromoterAI		0.042	Neutral
Mutation Taster		=299/1	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

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

Other links and lift over

dbSNP: rs2272903;

hg19: chr6-50786571;

COSMIC: COSV53831805;

COSMIC: COSV53831805;