rs303050

Variant names:

• chr6-10402950-T-C
• rs303050
• NM_001372066.1:c.771-340A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001372066.1(TFAP2A):​c.771-340A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 152,146 control chromosomes in the GnomAD database, including 10,943 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.31 (10943 hom., cov: 33)
• Consequence: TFAP2A NM_001372066.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.226
• Publications: 12 publications found

Genes affected

TFAP2A (HGNC:11742): (transcription factor AP-2 alpha) The protein encoded by this gene is a transcription factor that binds the consensus sequence 5'-GCCNNNGGC-3'. The encoded protein functions as either a homodimer or as a heterodimer with similar family members. This protein activates the transcription of some genes while inhibiting the transcription of others. Defects in this gene are a cause of branchiooculofacial syndrome (BOFS). Three transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Dec 2009]

TFAP2A Gene-Disease associations (from GenCC):

• branchiooculofacial syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, G2P, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 6-10402950-T-C is Benign according to our data. Variant chr6-10402950-T-C is described in ClinVar as Benign. ClinVar VariationId is 1262219.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001372066.1. 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
	TFAP2A	NM_001372066.1	MANE Select	c.771-340A>G		intron	N/A	NP_001358995.1	A0A6E1XE14
	TFAP2A	NM_001042425.3		c.753-340A>G		intron	N/A	NP_001035890.1	P05549-6
	TFAP2A	NM_001032280.3		c.747-340A>G		intron	N/A	NP_001027451.1	P05549-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFAP2A	ENST00000379613.10	TSL:1 MANE Select	c.771-340A>G		intron	N/A	ENSP00000368933.5	A0A6E1XE14
	TFAP2A	ENST00000379608.9	TSL:1	c.747-340A>G		intron	N/A	ENSP00000368928.3	P05549-5
	TFAP2A	ENST00000466073.5	TSL:1	c.765-340A>G		intron	N/A	ENSP00000417495.1	C1K3N0

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46349 AN: 152028 Hom.: 10902 Cov.: 33

Gnomad AFR AF: 0.654

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.297

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

GnomAD4 genome AF: 0.305 AC: 46448 AN: 152146 Hom.: 10943 Cov.: 33 AF XY: 0.300 AC XY: 22310 AN XY: 74374

African (AFR) AF: 0.655 AC: 27138 AN: 41454

American (AMR) AF: 0.254 AC: 3880 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 926 AN: 3472

East Asian (EAS) AF: 0.301 AC: 1558 AN: 5174

South Asian (SAS) AF: 0.119 AC: 577 AN: 4832

European-Finnish (FIN) AF: 0.122 AC: 1295 AN: 10604

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.150 AC: 10201 AN: 68000

Other (OTH) AF: 0.293 AC: 620 AN: 2116

Alfa AF: 0.212 Hom.: 6257

Bravo AF: 0.335

Asia WGS AF: 0.199 AC: 692 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	15
DANN	Benign	0.77
PhyloP100		0.23
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

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

Other links and lift over

dbSNP: rs303050;

hg19: chr6-10403183;