rs9841504

Variant names:

• chr3-114643917-C-G
• rs9841504
• NM_001348800.3:c.-295+49611G>C

Your query was ambiguous. Multiple possible variants found:

• chr3-114643917-C-G
• chr3-114643917-C-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.-295+49611G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 151,942 control chromosomes in the GnomAD database, including 2,462 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 0.15 (2462 hom., cov: 32)
• Consequence: ZBTB20 NM_001348800.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.23
• Publications: 53 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 = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZBTB20	NM_001348800.3	c.-295+49611G>C		intron_variant	Intron 6 of 11	ENST00000675478.1	NP_001335729.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZBTB20	ENST00000675478.1	c.-295+49611G>C		intron_variant	Intron 6 of 11		NM_001348800.3	ENSP00000501561.1

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23120 AN: 151824 Hom.: 2447 Cov.: 32

Gnomad AFR AF: 0.284

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.0704

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.0800

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0771

Gnomad OTH AF: 0.124

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

GnomAD4 genome AF: 0.153 AC: 23183 AN: 151942 Hom.: 2462 Cov.: 32 AF XY: 0.155 AC XY: 11516 AN XY: 74272

African (AFR) AF: 0.285 AC: 11789 AN: 41414

American (AMR) AF: 0.206 AC: 3139 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.0704 AC: 244 AN: 3468

East Asian (EAS) AF: 0.158 AC: 817 AN: 5180

South Asian (SAS) AF: 0.163 AC: 786 AN: 4824

European-Finnish (FIN) AF: 0.0800 AC: 846 AN: 10576

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0771 AC: 5235 AN: 67918

Other (OTH) AF: 0.126 AC: 265 AN: 2110

Alfa AF: 0.0936 Hom.: 476

Bravo AF: 0.166

Asia WGS AF: 0.185 AC: 644 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.054
DANN	Benign	0.72
PhyloP100		-2.2
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: rs9841504; hg19: chr3-114362764;