chr6-10404471-C-CGCGGG

Position:

• chr6-10404471-C-CGCGGG

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TFAP2A	NM_001372066.1	c.770+32_770+36dupCCCGC		intron_variant		ENST00000379613.10	NP_001358995.1
TFAP2A	NM_001042425.3	c.752+32_752+36dupCCCGC		intron_variant			NP_001035890.1
TFAP2A	NM_001032280.3	c.746+32_746+36dupCCCGC		intron_variant			NP_001027451.1
TFAP2A-AS2	NR_145448.1	n.-31_-30insGCGGG		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TFAP2A	ENST00000379613.10	c.770+36_770+37insCCCGC		intron_variant		1	NM_001372066.1	ENSP00000368933.5

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

GnomAD3 exomes AF: 0.00145 AC: 137 AN: 94340 Hom.: 3 AF XY: 0.00113 AC XY: 60 AN XY: 52936

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 SAS exome AF: 0.000568

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

Gnomad4 AFR exome AF: 0.0643

Gnomad4 AMR exome AF: 0.00430

Gnomad4 ASJ exome AF: 0.000698

Gnomad4 EAS exome AF: 0.000700

Gnomad4 SAS exome AF: 0.000659

Gnomad4 FIN exome AF: 0.000114

Gnomad4 NFE exome AF: 0.000420

Gnomad4 OTH exome AF: 0.00462

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

Gnomad4 AFR AF: 0.0655

Gnomad4 AMR AF: 0.00556

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00136

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000750

Gnomad4 OTH AF: 0.0138

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 14, 2018

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs564179777; hg19: chr6-10404704;