rs7643975

Variant names:

• chr3-114502975-C-T
• rs7643975
• NM_001348800.3:c.-294-2584G>A

Variant summary

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

The NM_001348800.3(ZBTB20):​c.-294-2584G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 152,052 control chromosomes in the GnomAD database, including 5,945 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 0.26 (5945 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: ZBTB20 NM_001348800.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.554
• Publications: 6 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-AS5 (HGNC:52841): (ZBTB20 antisense RNA 5)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.408 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.-294-2584G>A		intron	N/A	NP_001335729.1	Q9HC78-1
	ZBTB20	NM_001348803.3		c.-353-2584G>A		intron	N/A	NP_001335732.1	Q9HC78-1
	ZBTB20	NM_001393393.1		c.-294-2584G>A		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.-294-2584G>A		intron	N/A	ENSP00000501561.1	Q9HC78-1
	ZBTB20	ENST00000474710.6	TSL:1	c.-474-2584G>A		intron	N/A	ENSP00000419153.1	Q9HC78-1
	ZBTB20	ENST00000357258.8	TSL:1	c.-349-2584G>A		intron	N/A	ENSP00000349803.3	Q9HC78-2

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39732 AN: 151934 Hom.: 5937 Cov.: 32

Gnomad AFR AF: 0.413

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.245

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

GnomAD4 genome AF: 0.262 AC: 39771 AN: 152052 Hom.: 5945 Cov.: 32 AF XY: 0.262 AC XY: 19476 AN XY: 74344

African (AFR) AF: 0.413 AC: 17104 AN: 41440

American (AMR) AF: 0.215 AC: 3279 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 621 AN: 3466

East Asian (EAS) AF: 0.143 AC: 743 AN: 5182

South Asian (SAS) AF: 0.253 AC: 1218 AN: 4818

European-Finnish (FIN) AF: 0.243 AC: 2561 AN: 10560

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.198 AC: 13483 AN: 67990

Other (OTH) AF: 0.242 AC: 513 AN: 2116

Alfa AF: 0.225 Hom.: 9065

Bravo AF: 0.264

Asia WGS AF: 0.195 AC: 681 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.71
DANN	Benign	0.17
PhyloP100		-0.55
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs7643975;

hg19: chr3-114221822;