rs5019252

Variant names:

• chr20-63746996-C-T
• rs5019252
• NM_001369741.1:c.1704G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001369741.1(ZBTB46):​c.1704G>A​(p.Glu568Glu) 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
• Publications: 19 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ZBTB46	NM_001369741.1	c.1704G>A	p.Glu568Glu	synonymous_variant	Exon 5 of 5	ENST00000245663.9	NP_001356670.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZBTB46	ENST00000245663.9	c.1704G>A	p.Glu568Glu	synonymous_variant	Exon 5 of 5	5	NM_001369741.1	ENSP00000245663.3
ZBTB46	ENST00000302995.2	c.1704G>A	p.Glu568Glu	synonymous_variant	Exon 5 of 7	2		ENSP00000303102.2
ZBTB46	ENST00000395104.5	c.1704G>A	p.Glu568Glu	synonymous_variant	Exon 4 of 4	2		ENSP00000378536.1

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

GnomAD2 exomes AF: 0.342 AC: 81633 AN: 238970 AF XY: 0.334

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 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

African (AFR) AF: 0.164 AC: 5486 AN: 33446

American (AMR) AF: 0.477 AC: 21298 AN: 44612

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 8741 AN: 26078

East Asian (EAS) AF: 0.370 AC: 14679 AN: 39656

South Asian (SAS) AF: 0.223 AC: 19193 AN: 86192

European-Finnish (FIN) AF: 0.378 AC: 17931 AN: 47490

Middle Eastern (MID) AF: 0.274 AC: 1576 AN: 5758

European-Non Finnish (NFE) AF: 0.342 AC: 379769 AN: 1111384

Other (OTH) AF: 0.325 AC: 19610 AN: 60288

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

African (AFR) AF: 0.176 AC: 7287 AN: 41518

American (AMR) AF: 0.371 AC: 5670 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 1168 AN: 3470

East Asian (EAS) AF: 0.376 AC: 1926 AN: 5122

South Asian (SAS) AF: 0.216 AC: 1040 AN: 4824

European-Finnish (FIN) AF: 0.378 AC: 4003 AN: 10596

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.340 AC: 23091 AN: 67908

Other (OTH) AF: 0.311 AC: 655 AN: 2108

Alfa AF: 0.327 Hom.: 4651

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
PhyloP100		-3.1
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: rs5019252; hg19: chr20-62378349; COSMIC: COSV55508884; COSMIC: COSV55508884;