rs61740197

Positions:

chr9-128179037-C-A

Variant summary

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

The NM_001131016.2(CIZ1):c.1170G>T(p.Gln390His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00693 in 1,613,994 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0052 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0071 ( 34 hom. )

Consequence

CIZ1
NM_001131016.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.68

Variant links:

Genes affected

CIZ1 (HGNC:16744): (CDKN1A interacting zinc finger protein 1) The protein encoded by this gene is a zinc finger DNA binding protein that interacts with CIP1, part of a complex with cyclin E. The encoded protein may regulate the cellular localization of CIP1. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

CIZ1 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=0.0034489334).

BP6

Variant 9-128179037-C-A is Benign according to our data. Variant chr9-128179037-C-A is described in ClinVar as [Benign]. Clinvar id is 240851.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128179037-C-A is described in Lovd as [Likely_benign].

BS2

High AC in GnomAd4 at 785 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CIZ1	NM_001131016.2 linkuse as main transcript	c.1170G>T	p.Gln390His	missense_variant	8/17	ENST00000372938.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CIZ1	ENST00000372938.10 linkuse as main transcript	c.1170G>T	p.Gln390His	missense_variant	8/17	1	NM_001131016.2	P2	Q9ULV3-1

Frequencies

GnomAD3 genomes

AF:

0.00516

AC:

785

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00137

Gnomad AMI

AF:

0.00989

Gnomad AMR

AF:

0.00281

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00546

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00889

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00428

AC:

1064

AN:

248812

Hom.:

AF XY:

0.00431

AC XY:

580

AN XY:

134722

show subpopulations

Gnomad AFR exome

AF:

0.00154

Gnomad AMR exome

AF:

0.00203

Gnomad ASJ exome

AF:

0.000698

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00422

Gnomad NFE exome

AF:

0.00751

Gnomad OTH exome

AF:

0.00573

GnomAD4 exome

AF:

0.00712

AC:

10402

AN:

1461652

Hom.:

Cov.:

AF XY:

0.00697

AC XY:

5068

AN XY:

727116

show subpopulations

Gnomad4 AFR exome

AF:

0.00114

Gnomad4 AMR exome

AF:

0.00242

Gnomad4 ASJ exome

AF:

0.000498

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00392

Gnomad4 NFE exome

AF:

0.00873

Gnomad4 OTH exome

AF:

0.00536

GnomAD4 genome

AF:

0.00515

AC:

785

AN:

152342

Hom.:

Cov.:

AF XY:

0.00477

AC XY:

355

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.00137

Gnomad4 AMR

AF:

0.00281

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00546

Gnomad4 NFE

AF:

0.00889

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00722

Hom.:

Bravo

AF:

0.00505

TwinsUK

AF:

0.00485

AC:

ALSPAC

AF:

0.00882

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00814

AC:

ExAC

AF:

0.00415

AC:

504

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00736

EpiControl

AF:

0.00842

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	May 01, 2022	CIZ1: BS1, BS2 -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

CIZ1-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 05, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Dystonic disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 16, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.012

.;T;T;.;T;T;T;.

Eigen

Benign

-0.92

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.089

LIST_S2

Benign

0.58

T;T;T;T;.;.;T;T

M_CAP

Benign

0.0047

MetaRNN

Benign

0.0034

T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

.;.;.;.;.;L;L;.

MutationTaster

Benign

1.0

D;D;N;N;N;N;N;N;N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.5

N;N;N;.;N;N;.;N

REVEL

Benign

0.018

Sift

Uncertain

0.010

D;D;T;.;D;D;.;D

Sift4G

Uncertain

0.033

D;D;T;T;D;T;T;D

Polyphen

0.61, 0.35

.;P;.;.;P;B;B;.

Vest4

0.20

MutPred

0.21

.;Loss of helix (P = 0.0444);.;.;Loss of helix (P = 0.0444);Loss of helix (P = 0.0444);Loss of helix (P = 0.0444);.;

MVP

0.38

MPC

0.26

ClinPred

0.0032

GERP RS

1.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

gMVP

0.19

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