17-7459769-T-C

Position:

• chr17-7459769-T-C

Variant summary

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

The NM_001128833.2(ZBTB4):​c.*2171A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 152,310 control chromosomes in the GnomAD database, including 10,032 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 0.36 (9999 hom., cov: 31)
  • Exomes 𝑓: 0.41 (33 hom.)
• Consequence: ZBTB4 NM_001128833.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.460

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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBTB4	NM_001128833.2	c.*2171A>G		3_prime_UTR_variant	4/4	ENST00000380599.9	NP_001122305.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZBTB4	ENST00000380599	c.*2171A>G		3_prime_UTR_variant	4/4	1	NM_001128833.2	ENSP00000369973.4
ZBTB4	ENST00000311403	c.*2171A>G		3_prime_UTR_variant	4/4	1		ENSP00000307858.4

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54576 AN: 151764 Hom.: 9988 Cov.: 31

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.365

GnomAD4 exome AF: 0.414 AC: 178 AN: 430 Hom.: 33 Cov.: 0 AF XY: 0.404 AC XY: 101 AN XY: 250

Gnomad4 FIN exome AF: 0.413

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.360 AC: 54610 AN: 151880 Hom.: 9999 Cov.: 31 AF XY: 0.363 AC XY: 26965 AN XY: 74204

Gnomad4 AFR AF: 0.353

Gnomad4 AMR AF: 0.352

Gnomad4 ASJ AF: 0.320

Gnomad4 EAS AF: 0.234

Gnomad4 SAS AF: 0.493

Gnomad4 FIN AF: 0.415

Gnomad4 NFE AF: 0.358

Gnomad4 OTH AF: 0.370

Alfa AF: 0.349 Hom.: 17503

Bravo AF: 0.353

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.2
DANN	Benign	0.57

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: rs9217; hg19: chr17-7363088;