Variant 17-7462265-C-T 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 ENST00000380599.9(ZBTB4):c.2717G>A(p.Arg906Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00183 in 1,613,748 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0031 ( 7 hom., cov: 33)

Exomes 𝑓: 0.0017 ( 31 hom. )

Consequence

ZBTB4
ENST00000380599.9 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.69

Variant links:

Genes affected

ZBTB4 (HGNC:23847): (zinc finger and BTB domain containing 4) Enables several functions, including DNA-binding transcription repressor activity, RNA polymerase II-specific; methyl-CpNpG binding activity; and sequence-specific DNA binding activity. Involved in cellular response to DNA damage stimulus and negative regulation of transcription by RNA polymerase II. Located in cytosol and nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

ZBTB4 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=0.0023826659).

BP6

Variant 17-7462265-C-T is Benign according to our data. Variant chr17-7462265-C-T is described in ClinVar as [Benign]. Clinvar id is 770262.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 464 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBTB4	NM_001128833.2 linkuse as main transcript	c.2717G>A	p.Arg906Gln	missense_variant	4/4	ENST00000380599.9	NP_001122305.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZBTB4	ENST00000380599.9 linkuse as main transcript	c.2717G>A	p.Arg906Gln	missense_variant	4/4	1	NM_001128833.2	ENSP00000369973	P1
ZBTB4	ENST00000311403.4 linkuse as main transcript	c.2717G>A	p.Arg906Gln	missense_variant	4/4	1		ENSP00000307858	P1

Frequencies

GnomAD3 genomes

AF:

0.00305

AC:

464

AN:

152012

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00511

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0305

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000633

Gnomad OTH

AF:

0.000959

GnomAD3 exomes

AF:

0.00516

AC:

1288

AN:

249536

Hom.:

AF XY:

0.00453

AC XY:

613

AN XY:

135292

show subpopulations

Gnomad AFR exome

AF:

0.000252

Gnomad AMR exome

AF:

0.0152

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000327

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0302

Gnomad NFE exome

AF:

0.000640

Gnomad OTH exome

AF:

0.00443

GnomAD4 exome

AF:

0.00171

AC:

2493

AN:

1461618

Hom.:

Cov.:

AF XY:

0.00162

AC XY:

1181

AN XY:

727102

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.0142

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000327

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0282

Gnomad4 NFE exome

AF:

0.000228

Gnomad4 OTH exome

AF:

0.00121

GnomAD4 genome

AF:

0.00305

AC:

464

AN:

152130

Hom.:

Cov.:

AF XY:

0.00411

AC XY:

306

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.00510

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0305

Gnomad4 NFE

AF:

0.000633

Gnomad4 OTH

AF:

0.000949

Alfa

AF:

0.000510

Hom.:

Bravo

AF:

0.00152

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000582

AC:

ExAC

AF:

0.00411

AC:

499

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

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	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 26, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0043

T;T

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.64

MetaRNN

Benign

0.0024

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.20

N;N

MutationTaster

Benign

0.97

N;N

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.40

N;N

REVEL

Benign

0.052

Sift

Uncertain

0.0020

D;D

Sift4G

Benign

0.10

T;T

Polyphen

0.0050

B;B

Vest4

0.21

MVP

0.043

MPC

1.1

ClinPred

0.031

GERP RS

1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.098

gMVP

0.25

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