rs1621700

Variant names:

• chr6-10419865-C-T
• rs1621700
• ENST00000718199.1:n.195+8531C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.17 (3072 hom., cov: 33)
• Consequence: TFAP2A-AS1 ENST00000718199.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.468
• Publications: 5 publications found

Genes affected

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

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TFAP2A	NM_001042425.3	c.-415G>A		upstream_gene_variant			NP_001035890.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TFAP2A-AS1	ENST00000718199.1	n.195+8531C>T		intron_variant	Intron 1 of 3
TFAP2A-AS1	ENST00000718201.1	n.284+4485C>T		intron_variant	Intron 2 of 3
TFAP2A	ENST00000319516.8	c.-415G>A		upstream_gene_variant		5		ENSP00000316516.4

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26136 AN: 152046 Hom.: 3066 Cov.: 33

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.: 33 AF XY: 0.175 AC XY: 13012 AN XY: 74368

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: 32 AN: 294

European-Non Finnish (NFE) AF: 0.218 AC: 14841 AN: 67980

Other (OTH) AF: 0.158 AC: 335 AN: 2114

Alfa AF: 0.204 Hom.: 5870

Bravo AF: 0.164

Asia WGS AF: 0.141 AC: 490 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 28, 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	-0.80
CADD	Benign	6.1
DANN	Benign	0.86
PhyloP100		0.47
PromoterAI		0.0010	Neutral

Splicing

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

Other links and lift over

dbSNP: rs1621700; hg19: chr6-10420098;