rs1274224

chr3-114734408-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001348800.3(ZBTB20):c.-342-40833C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 151,900 control chromosomes in the GnomAD database, including 1,331 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 0.12 (1331 hom., cov: 32)
• Consequence: ZBTB20 NM_001348800.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0230

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZBTB20	NM_001348800.3	c.-342-40833C>T		intron_variant		ENST00000675478.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZBTB20	ENST00000675478.1	c.-342-40833C>T		intron_variant			NM_001348800.3	A2

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18107 AN: 151782 Hom.: 1328 Cov.: 32

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.0855

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.0191

Gnomad SAS AF: 0.0928

Gnomad FIN AF: 0.0345

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.0934

Gnomad OTH AF: 0.106

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

GnomAD4 genome AF: 0.119 AC: 18134 AN: 151900 Hom.: 1331 Cov.: 32 AF XY: 0.114 AC XY: 8459 AN XY: 74220

Gnomad4 AFR AF: 0.207

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.0190

Gnomad4 SAS AF: 0.0922

Gnomad4 FIN AF: 0.0345

Gnomad4 NFE AF: 0.0934

Gnomad4 OTH AF: 0.105

Alfa AF: 0.0984 Hom.: 825

Bravo AF: 0.129

Asia WGS AF: 0.0680 AC: 238 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	2.2
Dann	Benign	0.68

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: rs1274224; hg19: chr3-114453255;