rs2733403

Variant names:

• chr3-114402915-A-G
• rs2733403
• NM_001348800.3:c.-254-13810T>C

Variant summary

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

The NM_001348800.3(ZBTB20):​c.-254-13810T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 152,062 control chromosomes in the GnomAD database, including 5,540 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 0.25 (5540 hom., cov: 32)
• Consequence: ZBTB20 NM_001348800.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.113
• Publications: 1 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: Genomics England PanelApp, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZBTB20	NM_001348800.3	c.-254-13810T>C		intron_variant	Intron 7 of 11	ENST00000675478.1	NP_001335729.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZBTB20	ENST00000675478.1	c.-254-13810T>C		intron_variant	Intron 7 of 11		NM_001348800.3	ENSP00000501561.1

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38725 AN: 151944 Hom.: 5526 Cov.: 32

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.0529

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.239

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

GnomAD4 genome AF: 0.255 AC: 38767 AN: 152062 Hom.: 5540 Cov.: 32 AF XY: 0.252 AC XY: 18754 AN XY: 74358

African (AFR) AF: 0.379 AC: 15719 AN: 41458

American (AMR) AF: 0.149 AC: 2277 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 966 AN: 3466

East Asian (EAS) AF: 0.0526 AC: 272 AN: 5170

South Asian (SAS) AF: 0.263 AC: 1268 AN: 4818

European-Finnish (FIN) AF: 0.257 AC: 2722 AN: 10584

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.218 AC: 14813 AN: 67970

Other (OTH) AF: 0.239 AC: 505 AN: 2112

Alfa AF: 0.225 Hom.: 6954

Bravo AF: 0.253

Asia WGS AF: 0.175 AC: 614 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.7
DANN	Benign	0.31
PhyloP100		-0.11
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: rs2733403; hg19: chr3-114121762;