rs2272903

chr6-50818858-G-Achr6-50818858-G-C

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The XR_007059923.1(LOC124901490):n.125+44C>T variant causes a intron, non coding transcript change. The variant allele was found at a frequency of 0.126 in 1,600,400 control chromosomes in the GnomAD database, including 15,106 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2795 hom., cov: 32)
  • Exomes 𝑓: 0.12 (12311 hom.)
• Consequence: LOC124901490 XR_007059923.1 intron, non_coding_transcript
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 6.23

Genes affected

LOC124901490 (HGNC:):

TFAP2B (HGNC:11743): (transcription factor AP-2 beta) This gene encodes a member of the AP-2 family of transcription factors. AP-2 proteins form homo- or hetero-dimers with other AP-2 family members and bind specific DNA sequences. They are thought to stimulate cell proliferation and suppress terminal differentiation of specific cell types during embryonic development. Specific AP-2 family members differ in their expression patterns and binding affinity for different promoters. This protein functions as both a transcriptional activator and repressor. Mutations in this gene result in autosomal dominant Char syndrome, suggesting that this gene functions in the differentiation of neural crest cell derivatives. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 6-50818858-G-A is Benign according to our data. Variant chr6-50818858-G-A is described in ClinVar as [Benign]. Clinvar id is 1273651.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC124901490	XR_007059923.1	n.125+44C>T		intron_variant, non_coding_transcript_variant
TFAP2B	NM_003221.4			upstream_gene_variant		ENST00000393655.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TFAP2B	ENST00000344788.7	c.-67G>A		5_prime_UTR_variant	1/4	3
TFAP2B	ENST00000393655.4			upstream_gene_variant		1	NM_003221.4	P1

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26273 AN: 151822 Hom.: 2792 Cov.: 32

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.0681

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.169

GnomAD3 exomes AF: 0.149 AC: 37476 AN: 250704 Hom.: 3292 AF XY: 0.149 AC XY: 20223 AN XY: 135502

Gnomad AFR exome AF: 0.295

Gnomad AMR exome AF: 0.118

Gnomad ASJ exome AF: 0.171

Gnomad EAS exome AF: 0.228

Gnomad SAS exome AF: 0.192

Gnomad FIN exome AF: 0.187

Gnomad NFE exome AF: 0.105

Gnomad OTH exome AF: 0.154

GnomAD4 exome AF: 0.122 AC: 176025 AN: 1448460 Hom.: 12311 Cov.: 28 AF XY: 0.123 AC XY: 88848 AN XY: 721588

Gnomad4 AFR exome AF: 0.299

Gnomad4 AMR exome AF: 0.121

Gnomad4 ASJ exome AF: 0.167

Gnomad4 EAS exome AF: 0.226

Gnomad4 SAS exome AF: 0.189

Gnomad4 FIN exome AF: 0.175

Gnomad4 NFE exome AF: 0.102

Gnomad4 OTH exome AF: 0.136

GnomAD4 genome AF: 0.173 AC: 26288 AN: 151940 Hom.: 2795 Cov.: 32 AF XY: 0.179 AC XY: 13294 AN XY: 74268

Gnomad4 AFR AF: 0.290

Gnomad4 AMR AF: 0.146

Gnomad4 ASJ AF: 0.176

Gnomad4 EAS AF: 0.207

Gnomad4 SAS AF: 0.192

Gnomad4 FIN AF: 0.192

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.168

Alfa AF: 0.128 Hom.: 1017

Bravo AF: 0.175

Asia WGS AF: 0.182 AC: 632 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Char syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
Cadd	Benign	21
Dann	Benign	0.93

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2272903; hg19: chr6-50786571; COSMIC: COSV53831805; COSMIC: COSV53831805;