Variant chr4-4303022-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_145291.4(ZBTB49):c.1186G>A(p.Ala396Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0104 in 1,613,982 control chromosomes in the GnomAD database, including 106 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A396V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0069 ( 4 hom., cov: 32)

Exomes 𝑓: 0.011 ( 102 hom. )

Consequence

ZBTB49
NM_145291.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.939

Variant links:

Genes affected

ZBTB49 (HGNC:19883): (zinc finger and BTB domain containing 49) Enables DNA-binding transcription factor binding activity; sequence-specific DNA binding activity; and transcription coactivator binding activity. Involved in negative regulation of cell population proliferation; positive regulation of transcription by RNA polymerase II; and regulation of cell cycle. Located in cytosol; microtubule cytoskeleton; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZBTB49 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0083274245).

BP6

Variant 4-4303022-G-A is Benign according to our data. Variant chr4-4303022-G-A is described in ClinVar as [Benign]. Clinvar id is 777803.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZBTB49	NM_145291.4 linkuse as main transcript	c.1186G>A	p.Ala396Thr	missense_variant	3/8	ENST00000337872.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZBTB49	ENST00000337872.9 linkuse as main transcript	c.1186G>A	p.Ala396Thr	missense_variant	3/8	1	NM_145291.4	P1	Q6ZSB9-1

Frequencies

GnomAD3 genomes

AF:

0.00686

AC:

1044

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00203

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00785

Gnomad ASJ

AF:

0.00548

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000831

Gnomad FIN

AF:

0.000754

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0115

Gnomad OTH

AF:

0.0120

GnomAD3 exomes

AF:

0.00735

AC:

1841

AN:

250396

Hom.:

AF XY:

0.00726

AC XY:

985

AN XY:

135618

show subpopulations

Gnomad AFR exome

AF:

0.00245

Gnomad AMR exome

AF:

0.00896

Gnomad ASJ exome

AF:

0.00834

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000491

Gnomad FIN exome

AF:

0.000739

Gnomad NFE exome

AF:

0.0116

Gnomad OTH exome

AF:

0.0113

GnomAD4 exome

AF:

0.0108

AC:

15779

AN:

1461712

Hom.:

102

Cov.:

AF XY:

0.0104

AC XY:

7560

AN XY:

727142

show subpopulations

Gnomad4 AFR exome

AF:

0.00212

Gnomad4 AMR exome

AF:

0.00954

Gnomad4 ASJ exome

AF:

0.00819

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000580

Gnomad4 FIN exome

AF:

0.00107

Gnomad4 NFE exome

AF:

0.0128

Gnomad4 OTH exome

AF:

0.0113

GnomAD4 genome

AF:

0.00686

AC:

1044

AN:

152270

Hom.:

Cov.:

AF XY:

0.00580

AC XY:

432

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.00202

Gnomad4 AMR

AF:

0.00784

Gnomad4 ASJ

AF:

0.00548

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000832

Gnomad4 FIN

AF:

0.000754

Gnomad4 NFE

AF:

0.0115

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.0106

Hom.:

Bravo

AF:

0.00794

TwinsUK

AF:

0.0124

AC:

ALSPAC

AF:

0.0106

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.0120

AC:

103

ExAC

AF:

0.00712

AC:

864

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.0129

EpiControl

AF:

0.0129

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 03, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.62

CADD

Benign

4.1

DANN

Benign

0.73

DEOGEN2

Benign

0.0016

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.84

MetaRNN

Benign

0.0083

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.060

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.19

REVEL

Benign

0.019

Sift

Benign

0.52

Sift4G

Benign

0.73

Polyphen

0.0080

Vest4

0.043

MVP

0.21

MPC

0.15

ClinPred

0.0035

GERP RS

3.6

Varity_R

0.021

gMVP

0.085

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