rs1506024

Variant names:

• chr3-115056115-T-C
• rs1506024
• NM_001348800.3:c.-507+15104A>G

Variant summary

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

The NM_001348800.3(ZBTB20):​c.-507+15104A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 151,908 control chromosomes in the GnomAD database, including 30,124 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 0.60 (30124 hom., cov: 31)
• Consequence: ZBTB20 NM_001348800.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20
• Publications: 4 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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.756 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.-507+15104A>G		intron	N/A	NP_001335729.1	Q9HC78-1
	ZBTB20	NM_001348803.3		c.-630+15104A>G		intron	N/A	NP_001335732.1	Q9HC78-1
	ZBTB20	NM_001164343.2		c.-666+15104A>G		intron	N/A	NP_001157815.1	Q9HC78-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB20	ENST00000675478.1	MANE Select	c.-507+15104A>G		intron	N/A	ENSP00000501561.1	Q9HC78-1
	ZBTB20	ENST00000474710.6	TSL:1	c.-687+15104A>G		intron	N/A	ENSP00000419153.1	Q9HC78-1
	ZBTB20	ENST00000357258.8	TSL:1	c.-561-81699A>G		intron	N/A	ENSP00000349803.3	Q9HC78-2

Frequencies

GnomAD3 genomes AF: 0.600 AC: 91081 AN: 151790 Hom.: 30129 Cov.: 31

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.879

Gnomad AMR AF: 0.609

Gnomad ASJ AF: 0.667

Gnomad EAS AF: 0.337

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.736

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.762

Gnomad OTH AF: 0.615

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

GnomAD4 genome AF: 0.600 AC: 91090 AN: 151908 Hom.: 30124 Cov.: 31 AF XY: 0.595 AC XY: 44154 AN XY: 74246

African (AFR) AF: 0.331 AC: 13705 AN: 41386

American (AMR) AF: 0.609 AC: 9286 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.667 AC: 2315 AN: 3472

East Asian (EAS) AF: 0.337 AC: 1740 AN: 5160

South Asian (SAS) AF: 0.470 AC: 2265 AN: 4822

European-Finnish (FIN) AF: 0.736 AC: 7784 AN: 10576

Middle Eastern (MID) AF: 0.582 AC: 170 AN: 292

European-Non Finnish (NFE) AF: 0.762 AC: 51737 AN: 67920

Other (OTH) AF: 0.610 AC: 1288 AN: 2110

Alfa AF: 0.683 Hom.: 77754

Bravo AF: 0.581

Asia WGS AF: 0.401 AC: 1392 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.67
DANN	Benign	0.74
PhyloP100		-1.2
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: rs1506024; hg19: chr3-114774962;