17-7467286-G-A

Position:

• chr17-7467286-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001128833.2(ZBTB4):​c.-39C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 983,610 control chromosomes in the GnomAD database, including 11,427 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 0.17 (2379 hom., cov: 32)
  • Exomes 𝑓: 0.15 (9048 hom.)
• Consequence: ZBTB4 NM_001128833.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0300

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBTB4	NM_001128833.2	c.-39C>T		5_prime_UTR_premature_start_codon_gain_variant	2/4	ENST00000380599.9	NP_001122305.1
ZBTB4	NM_001128833.2	c.-39C>T		5_prime_UTR_variant	2/4	ENST00000380599.9	NP_001122305.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZBTB4	ENST00000380599.9	c.-39C>T		5_prime_UTR_premature_start_codon_gain_variant	2/4	1	NM_001128833.2	ENSP00000369973.4
ZBTB4	ENST00000311403.4	c.-39C>T		5_prime_UTR_premature_start_codon_gain_variant	2/4	1		ENSP00000307858.4
ZBTB4	ENST00000380599.9	c.-39C>T		5_prime_UTR_variant	2/4	1	NM_001128833.2	ENSP00000369973.4
ZBTB4	ENST00000311403.4	c.-39C>T		5_prime_UTR_variant	2/4	1		ENSP00000307858.4

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25116 AN: 151984 Hom.: 2363 Cov.: 32

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.142

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.0994

Gnomad EAS AF: 0.213

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.149

GnomAD4 exome AF: 0.145 AC: 120953 AN: 831508 Hom.: 9048 Cov.: 19 AF XY: 0.146 AC XY: 55933 AN XY: 384260

Gnomad4 AFR exome AF: 0.127

Gnomad4 AMR exome AF: 0.233

Gnomad4 ASJ exome AF: 0.0940

Gnomad4 EAS exome AF: 0.203

Gnomad4 SAS exome AF: 0.224

Gnomad4 FIN exome AF: 0.279

Gnomad4 NFE exome AF: 0.144

Gnomad4 OTH exome AF: 0.155

GnomAD4 genome AF: 0.165 AC: 25148 AN: 152102 Hom.: 2379 Cov.: 32 AF XY: 0.174 AC XY: 12968 AN XY: 74344

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.198

Gnomad4 ASJ AF: 0.0994

Gnomad4 EAS AF: 0.213

Gnomad4 SAS AF: 0.219

Gnomad4 FIN AF: 0.310

Gnomad4 NFE AF: 0.149

Gnomad4 OTH AF: 0.157

Alfa AF: 0.140 Hom.: 3092

Bravo AF: 0.154

Asia WGS AF: 0.281 AC: 976 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	10
DANN	Benign	0.88
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs3853894; hg19: chr17-7370605; COSMIC: COSV60984968;