rs9882269

Variant names:

• chr3-114443876-A-C
• rs9882269
• NM_001348800.3:c.-254-54771T>G

Your query was ambiguous. Multiple possible variants found:

• chr3-114443876-A-C
• chr3-114443876-A-T

Variant summary

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

The NM_001348800.3(ZBTB20):​c.-254-54771T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 152,140 control chromosomes in the GnomAD database, including 28,436 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 0.57 (28436 hom., cov: 33)
• Consequence: ZBTB20 NM_001348800.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.36
• Publications: 3 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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.741 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.-254-54771T>G		intron	N/A	NP_001335729.1	Q9HC78-1
	ZBTB20	NM_001348803.3		c.-313-54771T>G		intron	N/A	NP_001335732.1	Q9HC78-1
	ZBTB20	NM_001393393.1		c.-254-54771T>G		intron	N/A	NP_001380322.1	Q9HC78-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB20	ENST00000675478.1	MANE Select	c.-254-54771T>G		intron	N/A	ENSP00000501561.1	Q9HC78-1
	ZBTB20	ENST00000474710.6	TSL:1	c.-434-54771T>G		intron	N/A	ENSP00000419153.1	Q9HC78-1
	ZBTB20	ENST00000357258.8	TSL:1	c.-309-54771T>G		intron	N/A	ENSP00000349803.3	Q9HC78-2

Frequencies

GnomAD3 genomes AF: 0.568 AC: 86413 AN: 152020 Hom.: 28447 Cov.: 33

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.738

Gnomad AMR AF: 0.525

Gnomad ASJ AF: 0.700

Gnomad EAS AF: 0.560

Gnomad SAS AF: 0.556

Gnomad FIN AF: 0.747

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.747

Gnomad OTH AF: 0.609

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

GnomAD4 genome AF: 0.568 AC: 86400 AN: 152140 Hom.: 28436 Cov.: 33 AF XY: 0.567 AC XY: 42148 AN XY: 74382

African (AFR) AF: 0.231 AC: 9614 AN: 41530

American (AMR) AF: 0.524 AC: 8005 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.700 AC: 2425 AN: 3466

East Asian (EAS) AF: 0.559 AC: 2887 AN: 5166

South Asian (SAS) AF: 0.556 AC: 2677 AN: 4818

European-Finnish (FIN) AF: 0.747 AC: 7917 AN: 10592

Middle Eastern (MID) AF: 0.565 AC: 165 AN: 292

European-Non Finnish (NFE) AF: 0.747 AC: 50759 AN: 67980

Other (OTH) AF: 0.604 AC: 1278 AN: 2116

Alfa AF: 0.692 Hom.: 158854

Bravo AF: 0.541

Asia WGS AF: 0.503 AC: 1747 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	11
DANN	Benign	0.55
PhyloP100		1.4
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: rs9882269; hg19: chr3-114162723;