Variant rs2232448 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_014797.3(ZBTB24):c.1552G>A(p.Ala518Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0267 in 1,614,114 control chromosomes in the GnomAD database, including 2,559 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.078 ( 1229 hom., cov: 32)

Exomes 𝑓: 0.021 ( 1330 hom. )

Consequence

ZBTB24
NM_014797.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.156

Variant links:

Genes affected

ZBTB24 (HGNC:21143): (zinc finger and BTB domain containing 24) Predicted to enable DNA-binding transcription factor activity and RNA polymerase II cis-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 hematopoietic progenitor cell differentiation. Predicted to be located in nucleus. Implicated in immunodeficiency-centromeric instability-facial anomalies syndrome 2. [provided by Alliance of Genome Resources, Apr 2022]

ZBTB24 links:

ZBTB24 (HGNC:):

ZBTB24 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0028230548).

BP6

Variant 6-109466393-C-T is Benign according to our data. Variant chr6-109466393-C-T is described in ClinVar as [Benign]. Clinvar id is 472200.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBTB24	NM_014797.3 linkuse as main transcript	c.1552G>A	p.Ala518Thr	missense_variant	7/7	ENST00000230122.4	NP_055612.2	O43167-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZBTB24	ENST00000230122.4 linkuse as main transcript	c.1552G>A	p.Ala518Thr	missense_variant	7/7	1	NM_014797.3	ENSP00000230122.4		O43167-1

Frequencies

GnomAD3 genomes

AF:

0.0776

AC:

11796

AN:

152104

Hom.:

1227

Cov.:

show subpopulations

Gnomad AFR

AF:

0.238

Gnomad AMI

AF:

0.0406

Gnomad AMR

AF:

0.0346

Gnomad ASJ

AF:

0.00835

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0168

Gnomad FIN

AF:

0.00631

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0160

Gnomad OTH

AF:

0.0537

GnomAD3 exomes

AF:

0.0294

AC:

7388

AN:

251468

Hom.:

526

AF XY:

0.0256

AC XY:

3481

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.244

Gnomad AMR exome

AF:

0.0182

Gnomad ASJ exome

AF:

0.0112

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0192

Gnomad FIN exome

AF:

0.00693

Gnomad NFE exome

AF:

0.0160

Gnomad OTH exome

AF:

0.0186

GnomAD4 exome

AF:

0.0214

AC:

31355

AN:

1461892

Hom.:

1330

Cov.:

AF XY:

0.0206

AC XY:

14987

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.247

Gnomad4 AMR exome

AF:

0.0187

Gnomad4 ASJ exome

AF:

0.0115

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0193

Gnomad4 FIN exome

AF:

0.00786

Gnomad4 NFE exome

AF:

0.0161

Gnomad4 OTH exome

AF:

0.0286

GnomAD4 genome

AF:

0.0776

AC:

11819

AN:

152222

Hom.:

1229

Cov.:

AF XY:

0.0742

AC XY:

5525

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.238

Gnomad4 AMR

AF:

0.0346

Gnomad4 ASJ

AF:

0.00835

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0160

Gnomad4 FIN

AF:

0.00631

Gnomad4 NFE

AF:

0.0160

Gnomad4 OTH

AF:

0.0536

Alfa

AF:

0.0286

Hom.:

451

Bravo

AF:

0.0866

TwinsUK

AF:

0.0175

AC:

ALSPAC

AF:

0.0135

AC:

ESP6500AA

AF:

0.236

AC:

1041

ESP6500EA

AF:

0.0150

AC:

129

ExAC

AF:

0.0342

AC:

4149

Asia WGS

AF:

0.0230

AC:

AN:

3478

EpiCase

AF:

0.0161

EpiControl

AF:

0.0135

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Immunodeficiency-centromeric instability-facial anomalies syndrome 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.85

BayesDel_noAF

Benign

-0.86

CADD

Benign

5.2

DANN

Benign

0.75

DEOGEN2

Benign

0.0056

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.18

MetaRNN

Benign

0.0028

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.42

PrimateAI

Benign

0.27

PROVEAN

Benign

0.31

REVEL

Benign

0.13

Sift

Benign

0.44

Sift4G

Benign

0.41

Polyphen

0.0

Vest4

0.016

MPC

0.16

ClinPred

0.0012

GERP RS

0.90

Varity_R

0.022

gMVP

0.23

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