Variant 8-76704578-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_024721.5(ZFHX4):c.490G>A(p.Ala164Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00193 in 1,613,932 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 10 hom. )

Consequence

ZFHX4
NM_024721.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.97

Variant links:

Genes affected

ZFHX4 (HGNC:30939): (zinc finger homeobox 4) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific 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 be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZFHX4 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=0.012676746).

BP6

Variant 8-76704578-G-A is Benign according to our data. Variant chr8-76704578-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 782751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 208 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZFHX4	NM_024721.5 linkuse as main transcript	c.490G>A	p.Ala164Thr	missense_variant	2/11	ENST00000651372.2
ZFHX4	NM_001410934.1 linkuse as main transcript	c.490G>A	p.Ala164Thr	missense_variant	2/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZFHX4	ENST00000651372.2 linkuse as main transcript	c.490G>A	p.Ala164Thr	missense_variant	2/11		NM_024721.5	P4	Q86UP3-5

Frequencies

GnomAD3 genomes

AF:

0.00137

AC:

208

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00229

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00118

AC:

292

AN:

248472

Hom.:

AF XY:

0.00122

AC XY:

164

AN XY:

134794

show subpopulations

Gnomad AFR exome

AF:

0.000129

Gnomad AMR exome

AF:

0.00116

Gnomad ASJ exome

AF:

0.000997

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.000372

Gnomad NFE exome

AF:

0.00198

Gnomad OTH exome

AF:

0.00133

GnomAD4 exome

AF:

0.00199

AC:

2903

AN:

1461632

Hom.:

Cov.:

AF XY:

0.00195

AC XY:

1415

AN XY:

727094

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.00134

Gnomad4 ASJ exome

AF:

0.00103

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.000487

Gnomad4 NFE exome

AF:

0.00241

Gnomad4 OTH exome

AF:

0.00152

GnomAD4 genome

AF:

0.00137

AC:

208

AN:

152300

Hom.:

Cov.:

AF XY:

0.00113

AC XY:

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.000553

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00229

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00212

Hom.:

Bravo

AF:

0.00140

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00285

AC:

ESP6500AA

AF:

0.00129

AC:

ESP6500EA

AF:

0.00145

AC:

ExAC

AF:

0.00121

AC:

146

EpiCase

AF:

0.00196

EpiControl

AF:

0.00190

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Invitae	Jul 06, 2018	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2022	ZFHX4: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

DANN

Uncertain

0.99

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.85

D;D;T

M_CAP

Benign

0.0094

MetaRNN

Benign

0.013

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

N;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.8

N;.;N

REVEL

Benign

0.13

Sift

Benign

0.081

T;.;T

Sift4G

Benign

0.22

T;.;T

Vest4

0.78

MVP

0.20

MPC

0.46

ClinPred

0.030

GERP RS

5.4

gMVP

0.49

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