dbSNP rs1621700: TFAP2A-AS1:n.195+8531C>T (chr6-10419865-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000718199.1(TFAP2A-AS1):n.195+8531C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 152,164 control chromosomes in the GnomAD database, including 3,072 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.17 ( 3072 hom., cov: 33)

Consequence

TFAP2A-AS1
ENST00000718199.1 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.468

Publications

5 publications found

Variant links:

Genes affected

TFAP2A-AS1 (HGNC:40579): (TFAP2A antisense RNA 1)

TFAP2A-AS1 links:

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: Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet, G2P

TFAP2A links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript ENST00000718199.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 6-10419865-C-T is Benign according to our data. Variant chr6-10419865-C-T is described in ClinVar as Benign. ClinVar VariationId is 1287998.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000718199.1. 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_001042425.3		c.-415G>A		upstream_gene	N/A	NP_001035890.1	P05549-6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TFAP2A-AS1	ENST00000718199.1		n.195+8531C>T	intron	N/A
TFAP2A-AS1	ENST00000718201.1		n.284+4485C>T	intron	N/A
TFAP2A	ENST00000319516.8	TSL:5	c.-415G>A	upstream_gene	N/A	ENSP00000316516.4	P05549-6

Frequencies

GnomAD3 genomes

AF:

0.172

AC:

26136

AN:

152046

Hom.:

3066

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0413

Gnomad AMI

AF:

0.117

Gnomad AMR

AF:

0.266

Gnomad ASJ

AF:

0.167

Gnomad EAS

AF:

0.0617

Gnomad SAS

AF:

0.196

Gnomad FIN

AF:

0.303

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.218

Gnomad OTH

AF:

0.160

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

GnomAD4 genome

AF:

0.172

AC:

26157

AN:

152164

Hom.:

3072

Cov.:

AF XY:

0.175

AC XY:

13012

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.0411

AC:

1709

AN:

41552

American (AMR)

AF:

0.267

AC:

4084

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.167

AC:

578

AN:

3470

East Asian (EAS)

AF:

0.0618

AC:

319

AN:

5162

South Asian (SAS)

AF:

0.197

AC:

949

AN:

4822

European-Finnish (FIN)

AF:

0.303

AC:

3204

AN:

10570

Middle Eastern (MID)

AF:

0.109

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.218

AC:

14841

AN:

67980

Other (OTH)

AF:

0.158

AC:

335

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1083

2166

3248

4331

5414

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

290

580

870

1160

1450

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.204

Hom.:

5870

Bravo

AF:

0.164

Asia WGS

AF:

0.141

AC:

490

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

6.1

(source)

DANN

Benign

0.86

PhyloP100

0.47

PromoterAI

0.0010

Neutral

(source)

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.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over