rs5019252

chr20-63746996-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001369741.1(ZBTB46):c.1704G>A(p.Glu568=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 1,606,946 control chromosomes in the GnomAD database, including 91,538 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 0.30 (7348 hom., cov: 32)
  • Exomes 𝑓: 0.34 (84190 hom.)
• Consequence: ZBTB46 NM_001369741.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.11

Genes affected

ZBTB46 (HGNC:16094): (zinc finger and BTB domain containing 46) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to act upstream of or within regulation of leukocyte differentiation. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP7: Synonymous conserved (PhyloP=-3.11 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZBTB46	NM_001369741.1	c.1704G>A	p.Glu568=	synonymous_variant	5/5	ENST00000245663.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZBTB46	ENST00000245663.9	c.1704G>A	p.Glu568=	synonymous_variant	5/5	5	NM_001369741.1	P1
ZBTB46	ENST00000302995.2	c.1704G>A	p.Glu568=	synonymous_variant	5/7	2		P1
ZBTB46	ENST00000395104.5	c.1704G>A	p.Glu568=	synonymous_variant	4/4	2		P1

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45219 AN: 151924 Hom.: 7341 Cov.: 32

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.375

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.310

GnomAD3 exomes AF: 0.342 AC: 81633 AN: 238970 Hom.: 14950 AF XY: 0.334 AC XY: 43720 AN XY: 130834

Gnomad AFR exome AF: 0.172

Gnomad AMR exome AF: 0.492

Gnomad ASJ exome AF: 0.334

Gnomad EAS exome AF: 0.361

Gnomad SAS exome AF: 0.220

Gnomad FIN exome AF: 0.375

Gnomad NFE exome AF: 0.345

Gnomad OTH exome AF: 0.334

GnomAD4 exome AF: 0.336 AC: 488283 AN: 1454904 Hom.: 84190 Cov.: 58 AF XY: 0.332 AC XY: 240041 AN XY: 724024

Gnomad4 AFR exome AF: 0.164

Gnomad4 AMR exome AF: 0.477

Gnomad4 ASJ exome AF: 0.335

Gnomad4 EAS exome AF: 0.370

Gnomad4 SAS exome AF: 0.223

Gnomad4 FIN exome AF: 0.378

Gnomad4 NFE exome AF: 0.342

Gnomad4 OTH exome AF: 0.325

GnomAD4 genome AF: 0.298 AC: 45258 AN: 152042 Hom.: 7348 Cov.: 32 AF XY: 0.297 AC XY: 22096 AN XY: 74292

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.371

Gnomad4 ASJ AF: 0.337

Gnomad4 EAS AF: 0.376

Gnomad4 SAS AF: 0.216

Gnomad4 FIN AF: 0.378

Gnomad4 NFE AF: 0.340

Gnomad4 OTH AF: 0.311

Alfa AF: 0.331 Hom.: 3348

Bravo AF: 0.300

Asia WGS AF: 0.289 AC: 1005 AN: 3478

EpiCase AF: 0.339

EpiControl AF: 0.334

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.011
Dann	Benign	0.76

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: rs5019252; hg19: chr20-62378349; COSMIC: COSV55508884; COSMIC: COSV55508884;