rs6804032

Variant names:

• chr3-114829624-C-T
• rs6804032
• NM_001348800.3:c.-416-28450G>A

Variant summary

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

The NM_001348800.3(ZBTB20):​c.-416-28450G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 151,780 control chromosomes in the GnomAD database, including 1,579 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 0.13 (1579 hom., cov: 32)
• Consequence: ZBTB20 NM_001348800.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.662
• Publications: 2 publications found

Genes affected

ZBTB20 (HGNC:13503): (zinc finger and BTB domain containing 20) This gene, which was initially designated as dendritic cell-derived BTB/POZ zinc finger (DPZF), belongs to a family of transcription factors with an N-terminal BTB/POZ domain and a C-terminal DNA-bindng zinc finger domain. The BTB/POZ domain is a hydrophobic region of approximately 120 aa which mediates association with other BTB/POZ domain-containing proteins. This gene acts as a transcriptional repressor and plays a role in many processes including neurogenesis, glucose homeostasis, and postnatal growth. Mutations in this gene have been associated with Primrose syndrome as well as the 3q13.31 microdeletion syndrome. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Feb 2017]

ZBTB20 Gene-Disease associations (from GenCC):

• Primrose syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Genomics England PanelApp, Ambry Genetics
• diabetes mellitus

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001348800.3. 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
	ZBTB20	NM_001348800.3	MANE Select	c.-416-28450G>A		intron	N/A	NP_001335729.1	Q9HC78-1
	ZBTB20	NM_001348803.3		c.-539-28450G>A		intron	N/A	NP_001335732.1	Q9HC78-1
	ZBTB20	NM_001164343.2		c.-506+44415G>A		intron	N/A	NP_001157815.1	Q9HC78-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB20	ENST00000675478.1	MANE Select	c.-416-28450G>A		intron	N/A	ENSP00000501561.1	Q9HC78-1
	ZBTB20	ENST00000474710.6	TSL:1	c.-596-28450G>A		intron	N/A	ENSP00000419153.1	Q9HC78-1
	ZBTB20	ENST00000357258.8	TSL:1	c.-471-28450G>A		intron	N/A	ENSP00000349803.3	Q9HC78-2

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19445 AN: 151662 Hom.: 1580 Cov.: 32

Gnomad AFR AF: 0.0496

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.0139

Gnomad SAS AF: 0.0688

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.158

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.128 AC: 19437 AN: 151780 Hom.: 1579 Cov.: 32 AF XY: 0.130 AC XY: 9640 AN XY: 74182

African (AFR) AF: 0.0495 AC: 2052 AN: 41460

American (AMR) AF: 0.143 AC: 2163 AN: 15176

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 809 AN: 3460

East Asian (EAS) AF: 0.0139 AC: 72 AN: 5162

South Asian (SAS) AF: 0.0691 AC: 333 AN: 4822

European-Finnish (FIN) AF: 0.245 AC: 2590 AN: 10572

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.160 AC: 10836 AN: 67812

Other (OTH) AF: 0.157 AC: 331 AN: 2110

Alfa AF: 0.147 Hom.: 1175

Bravo AF: 0.117

Asia WGS AF: 0.0590 AC: 211 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.5
DANN	Benign	0.58
PhyloP100		-0.66
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6804032; hg19: chr3-114548471;