6-10419243-C-T

Position:

• chr6-10419243-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.426

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 ClinVar 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/exons	MANE	Protein	UniProt
TFAP2A	NM_001042425.3	c.33+175G>A		intron_variant			NP_001035890.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TFAP2A	ENST00000319516.8	c.33+175G>A		intron_variant		5		ENSP00000316516.4
TFAP2A	ENST00000464323.1	n.137+175G>A		intron_variant		2
TFAP2A	ENST00000473652.1	n.242+175G>A		intron_variant		3
TFAP2A	ENST00000486038.1	n.206+175G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.613 AC: 93076 AN: 151942 Hom.: 29683 Cov.: 33

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.: 33 AF XY: 0.614 AC XY: 45651 AN XY: 74318

Gnomad4 AFR AF: 0.794

Gnomad4 AMR AF: 0.622

Gnomad4 ASJ AF: 0.481

Gnomad4 EAS AF: 0.618

Gnomad4 SAS AF: 0.661

Gnomad4 FIN AF: 0.559

Gnomad4 NFE AF: 0.518

Gnomad4 OTH AF: 0.563

Alfa AF: 0.535 Hom.: 31448

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

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.9
DANN	Benign	0.88

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs303055; hg19: chr6-10419476; COSMIC: COSV60237473; COSMIC: COSV60237473;