Genetic Variant TFAP2A:c.33+175G>A (chr6-10419243-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 NM_001042425.3(TFAP2A):c.33+175G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.613 in 152,060 control chromosomes in the GnomAD database, including 29,733 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.61 ( 29733 hom., cov: 33)

Consequence

TFAP2A
NM_001042425.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.426

Publications

6 publications found

Variant links:

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 links:

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

TFAP2A-AS1 links:

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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=-0.79).

BP6

Variant 6-10419243-C-T is Benign according to our data. Variant chr6-10419243-C-T is described in CliVar as Benign. Clinvar id is 1278327.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-10419243-C-T is described in CliVar as Benign. Clinvar id is 1278327.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.787 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TFAP2A	NM_001042425.3 link	c.33+175G>A		intron_variant	Intron 1 of 6		NP_001035890.1	P05549-6

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
TFAP2A	ENST00000319516.8 link	c.33+175G>A	intron_variant	Intron 1 of 6	5	ENSP00000316516.4	P05549-6
TFAP2A	ENST00000464323.1 link	n.137+175G>A	intron_variant	Intron 1 of 1	2
TFAP2A	ENST00000473652.1 link	n.242+175G>A	intron_variant	Intron 1 of 4	3

Frequencies

GnomAD3 genomes

AF:

0.613

AC:

93076

AN:

151942

Hom.:

29683

Cov.:

show subpopulations

Gnomad AFR

AF:

0.793

Gnomad AMI

AF:

0.286

Gnomad AMR

AF:

0.621

Gnomad ASJ

AF:

0.481

Gnomad EAS

AF:

0.617

Gnomad SAS

AF:

0.661

Gnomad FIN

AF:

0.559

Gnomad MID

AF:

0.506

Gnomad NFE

AF:

0.518

Gnomad OTH

AF:

0.568

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

GnomAD4 genome

AF:

0.613

AC:

93184

AN:

152060

Hom.:

29733

Cov.:

AF XY:

0.614

AC XY:

45651

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.794

AC:

32944

AN:

41502

American (AMR)

AF:

0.622

AC:

9503

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.481

AC:

1667

AN:

3468

East Asian (EAS)

AF:

0.618

AC:

3172

AN:

5132

South Asian (SAS)

AF:

0.661

AC:

3188

AN:

4820

European-Finnish (FIN)

AF:

0.559

AC:

5915

AN:

10584

Middle Eastern (MID)

AF:

0.507

AC:

149

AN:

294

European-Non Finnish (NFE)

AF:

0.518

AC:

35198

AN:

67948

Other (OTH)

AF:

0.563

AC:

1188

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1772

3543

5315

7086

8858

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

766

1532

2298

3064

3830

<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:

0.543

Hom.:

44997

Bravo

AF:

0.624

Asia WGS

AF:

0.621

AC:

2161

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 29, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

2.9

(source)

DANN

Benign

0.88

PhyloP100

-0.43

PromoterAI

-0.0095

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over