Genetic Variant ZBTB2:p.Glu432Glu (chr6-151365770-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_020861.3(ZBTB2):c.1296G>A(p.Glu432Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 1,613,910 control chromosomes in the GnomAD database, including 295,435 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.54 ( 23512 hom., cov: 32)

Exomes 𝑓: 0.60 ( 271923 hom. )

Consequence

ZBTB2
NM_020861.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.458

Variant links:

Genes affected

ZBTB2 (HGNC:20868): (zinc finger and BTB domain containing 2) Enables DNA-binding transcription repressor activity, RNA polymerase II-specific; RNA polymerase II cis-regulatory region sequence-specific DNA binding activity; and identical protein binding activity. Involved in negative regulation of transcription by RNA polymerase II. Predicted to be active in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZBTB2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 6-151365770-C-T is Benign according to our data. Variant chr6-151365770-C-T is described in ClinVar as [Benign]. Clinvar id is 1286394.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.458 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZBTB2	NM_020861.3 link	c.1296G>A	p.Glu432Glu	synonymous_variant	Exon 3 of 3	ENST00000325144.5	NP_065912.1	Q8N680

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZBTB2	ENST00000325144.5 link	c.1296G>A	p.Glu432Glu	synonymous_variant	Exon 3 of 3	1	NM_020861.3	ENSP00000323183.4		Q8N680

Frequencies

GnomAD3 genomes

AF:

0.541

AC:

82180

AN:

151934

Hom.:

23510

Cov.:

show subpopulations

Gnomad AFR

AF:

0.391

Gnomad AMI

AF:

0.421

Gnomad AMR

AF:

0.557

Gnomad ASJ

AF:

0.589

Gnomad EAS

AF:

0.294

Gnomad SAS

AF:

0.378

Gnomad FIN

AF:

0.677

Gnomad MID

AF:

0.440

Gnomad NFE

AF:

0.637

Gnomad OTH

AF:

0.539

GnomAD3 exomes

AF:

0.554

AC:

139177

AN:

251332

Hom.:

40667

AF XY:

0.549

AC XY:

74589

AN XY:

135840

show subpopulations

Gnomad AFR exome

AF:

0.390

Gnomad AMR exome

AF:

0.583

Gnomad ASJ exome

AF:

0.591

Gnomad EAS exome

AF:

0.280

Gnomad SAS exome

AF:

0.384

Gnomad FIN exome

AF:

0.675

Gnomad NFE exome

AF:

0.630

Gnomad OTH exome

AF:

0.580

GnomAD4 exome

AF:

0.603

AC:

881746

AN:

1461858

Hom.:

271923

Cov.:

AF XY:

0.597

AC XY:

434157

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.380

Gnomad4 AMR exome

AF:

0.578

Gnomad4 ASJ exome

AF:

0.591

Gnomad4 EAS exome

AF:

0.354

Gnomad4 SAS exome

AF:

0.383

Gnomad4 FIN exome

AF:

0.669

Gnomad4 NFE exome

AF:

0.637

Gnomad4 OTH exome

AF:

0.567

GnomAD4 genome

AF:

0.541

AC:

82216

AN:

152052

Hom.:

23512

Cov.:

AF XY:

0.538

AC XY:

39991

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.391

Gnomad4 AMR

AF:

0.557

Gnomad4 ASJ

AF:

0.589

Gnomad4 EAS

AF:

0.295

Gnomad4 SAS

AF:

0.379

Gnomad4 FIN

AF:

0.677

Gnomad4 NFE

AF:

0.637

Gnomad4 OTH

AF:

0.533

Alfa

AF:

0.606

Hom.:

64159

Bravo

AF:

0.528

Asia WGS

AF:

0.338

AC:

1180

AN:

3478

EpiCase

AF:

0.622

EpiControl

AF:

0.625

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 15, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

8.7

DANN

Benign

0.50

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over