6-10419243-C-T

Variant names:

• chr6-10419243-C-T
• rs303055
• NM_001042425.3:c.33+175G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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-AS1 (HGNC:40579): (TFAP2A antisense RNA 1)

ACMG classification

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 ClinVar as Benign. ClinVar VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042425.3. 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_001042425.3		c.33+175G>A		intron	N/A	NP_001035890.1	P05549-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFAP2A	ENST00000319516.8	TSL:5	c.33+175G>A		intron	N/A	ENSP00000316516.4	P05549-6
	TFAP2A	ENST00000464323.1	TSL:2	n.137+175G>A		intron	N/A
	TFAP2A	ENST00000473652.1	TSL:3	n.242+175G>A		intron	N/A

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

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

Alfa AF: 0.543 Hom.: 44997

Bravo AF: 0.624

Asia WGS AF: 0.621 AC: 2161 AN: 3478

ClinVar

ClinVar submissions as Germline

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
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.9
DANN	Benign	0.88
PhyloP100		-0.43
PromoterAI		-0.0095	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

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