6-10404471-CGCGGG-CGCGGGGCGGG

Variant names:

• chr6-10404471-C-CGCGGG
• rs564179777
• NM_001372066.1:c.770+32_770+36dupCCCGC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001372066.1(TFAP2A):​c.770+32_770+36dupCCCGC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00379 in 1,450,054 control chromosomes in the GnomAD database, including 139 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.019 (81 hom., cov: 33)
  • Exomes 𝑓: 0.0020 (58 hom.)
• Consequence: TFAP2A NM_001372066.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.19
• Publications: 0 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-AS2 (HGNC:52289): (TFAP2A antisense RNA 2) The product of this intronless gene is a capped lncRNA that is nuclear-enriched and associated with chromatin. The encoded transcript may be involved in the regulation of developmental gene expression in a context-dependent manner, functioning as a repressor in non-pluripotent cells and an activator in pluripotent cells. Transcription of this gene is activated in 8-cell human embryos during the major wave of zygotic genome activation, independently of and prior to the activation of TFAP2A, an overlapping gene found on the opposite strand. Expression of this gene is characterized by high cell-to-cell variability in the cells of totipotent human embryos and in stable cell lines. [provided by RefSeq, Mar 2017]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 6-10404471-C-CGCGGG is Benign according to our data. Variant chr6-10404471-C-CGCGGG is described in ClinVar as Benign. ClinVar VariationId is 1178438.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0635 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.770+32_770+36dupCCCGC		intron	N/A	NP_001358995.1	A0A6E1XE14
	TFAP2A	NM_001042425.3		c.752+32_752+36dupCCCGC		intron	N/A	NP_001035890.1	P05549-6
	TFAP2A	NM_001032280.3		c.746+32_746+36dupCCCGC		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.770+32_770+36dupCCCGC		intron	N/A	ENSP00000368933.5	A0A6E1XE14
	TFAP2A	ENST00000379608.9	TSL:1	c.746+32_746+36dupCCCGC		intron	N/A	ENSP00000368928.3	P05549-5
	TFAP2A	ENST00000466073.5	TSL:1	c.764+32_764+36dupCCCGC		intron	N/A	ENSP00000417495.1	C1K3N0

Frequencies

GnomAD3 genomes AF: 0.0190 AC: 2890 AN: 151994 Hom.: 81 Cov.: 33

Gnomad AFR AF: 0.0655

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00557

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00136

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.000750

Gnomad OTH AF: 0.0139

GnomAD2 exomes AF: 0.00145 AC: 137 AN: 94340 AF XY: 0.00113

Gnomad AFR exome AF: 0.0337

Gnomad AMR exome AF: 0.00289

Gnomad ASJ exome AF: 0.000189

Gnomad EAS exome AF: 0.000407

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000221

Gnomad OTH exome AF: 0.00164

GnomAD4 exome AF: 0.00200 AC: 2601 AN: 1297954 Hom.: 58 Cov.: 25 AF XY: 0.00182 AC XY: 1158 AN XY: 637194

African (AFR) AF: 0.0643 AC: 1702 AN: 26482

American (AMR) AF: 0.00430 AC: 111 AN: 25838

Ashkenazi Jewish (ASJ) AF: 0.000698 AC: 15 AN: 21492

East Asian (EAS) AF: 0.000700 AC: 21 AN: 29994

South Asian (SAS) AF: 0.000659 AC: 44 AN: 66808

European-Finnish (FIN) AF: 0.000114 AC: 5 AN: 43976

Middle Eastern (MID) AF: 0.00585 AC: 26 AN: 4448

European-Non Finnish (NFE) AF: 0.000420 AC: 431 AN: 1025680

Other (OTH) AF: 0.00462 AC: 246 AN: 53236

GnomAD4 genome AF: 0.0190 AC: 2896 AN: 152100 Hom.: 81 Cov.: 33 AF XY: 0.0180 AC XY: 1339 AN XY: 74358

African (AFR) AF: 0.0655 AC: 2719 AN: 41506

American (AMR) AF: 0.00556 AC: 85 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00136 AC: 7 AN: 5142

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00685 AC: 2 AN: 292

European-Non Finnish (NFE) AF: 0.000750 AC: 51 AN: 67970

Other (OTH) AF: 0.0138 AC: 29 AN: 2108

Alfa AF: 0.00103 Hom.: 0

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
PhyloP100		2.2
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs564179777; hg19: chr6-10404704;