chr3-114616176-T-C

Variant names:

• chr3-114616176-T-C
• rs2669892
• NM_001348800.3:c.-295+77352A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001348800.3(ZBTB20):​c.-295+77352A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 152,078 control chromosomes in the GnomAD database, including 7,542 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 0.28 (7542 hom., cov: 32)
• Consequence: ZBTB20 NM_001348800.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.15
• Publications: 5 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.488 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.-295+77352A>G		intron	N/A	NP_001335729.1
	ZBTB20	NM_001348803.3		c.-417-33074A>G		intron	N/A	NP_001335732.1
	ZBTB20	NM_001393393.1		c.-295+77352A>G		intron	N/A	NP_001380322.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB20	ENST00000675478.1	MANE Select	c.-295+77352A>G		intron	N/A	ENSP00000501561.1
	ZBTB20	ENST00000474710.6	TSL:1	c.-475+77352A>G		intron	N/A	ENSP00000419153.1
	ZBTB20	ENST00000357258.8	TSL:1	c.-350+77352A>G		intron	N/A	ENSP00000349803.3

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42738 AN: 151960 Hom.: 7528 Cov.: 32

Gnomad AFR AF: 0.494

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.0391

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.286

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

GnomAD4 genome AF: 0.281 AC: 42796 AN: 152078 Hom.: 7542 Cov.: 32 AF XY: 0.274 AC XY: 20354 AN XY: 74364

African (AFR) AF: 0.494 AC: 20463 AN: 41430

American (AMR) AF: 0.184 AC: 2816 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 992 AN: 3464

East Asian (EAS) AF: 0.0392 AC: 203 AN: 5182

South Asian (SAS) AF: 0.120 AC: 577 AN: 4818

European-Finnish (FIN) AF: 0.204 AC: 2159 AN: 10590

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.218 AC: 14828 AN: 67994

Other (OTH) AF: 0.290 AC: 611 AN: 2110

Alfa AF: 0.228 Hom.: 2649

Bravo AF: 0.290

Asia WGS AF: 0.131 AC: 457 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	21
DANN	Benign	0.76
PhyloP100		3.2
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: rs2669892; hg19: chr3-114335023;