rs4796420

Variant names:

• chr17-7476298-T-A
• rs4796420
• NM_001128833.2:c.-81+3158A>T

Variant summary

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

The NM_001128833.2(ZBTB4):​c.-81+3158A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,164 control chromosomes in the GnomAD database, including 3,074 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 0.20 (3074 hom., cov: 32)
• Consequence: ZBTB4 NM_001128833.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.664
• Publications: 10 publications found

Genes affected

ZBTB4 (HGNC:23847): (zinc finger and BTB domain containing 4) Enables several functions, including DNA-binding transcription repressor activity, RNA polymerase II-specific; methyl-CpNpG binding activity; and sequence-specific DNA binding activity. Involved in cellular response to DNA damage stimulus and negative regulation of transcription by RNA polymerase II. Located in cytosol and nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

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 (SAS) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZBTB4	NM_001128833.2	c.-81+3158A>T		intron_variant	Intron 1 of 3	ENST00000380599.9	NP_001122305.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZBTB4	ENST00000380599.9	c.-81+3158A>T		intron_variant	Intron 1 of 3	1	NM_001128833.2	ENSP00000369973.4
ZBTB4	ENST00000311403.4	c.-81+7706A>T		intron_variant	Intron 1 of 3	1		ENSP00000307858.4

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29756 AN: 152046 Hom.: 3078 Cov.: 32

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.290

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.0337

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.214

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

GnomAD4 genome AF: 0.196 AC: 29762 AN: 152164 Hom.: 3074 Cov.: 32 AF XY: 0.192 AC XY: 14299 AN XY: 74400

African (AFR) AF: 0.213 AC: 8844 AN: 41486

American (AMR) AF: 0.152 AC: 2326 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 775 AN: 3472

East Asian (EAS) AF: 0.0337 AC: 175 AN: 5186

South Asian (SAS) AF: 0.280 AC: 1347 AN: 4816

European-Finnish (FIN) AF: 0.140 AC: 1481 AN: 10602

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.206 AC: 14025 AN: 67998

Other (OTH) AF: 0.212 AC: 447 AN: 2112

Alfa AF: 0.201 Hom.: 388

Bravo AF: 0.198

Asia WGS AF: 0.149 AC: 519 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.9
DANN	Benign	0.79
PhyloP100		0.66
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: rs4796420; hg19: chr17-7379617;