Variant 9-128166354-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001131016.2(CIZ1):c.2540G>A(p.Arg847Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0227 in 1,561,462 control chromosomes in the GnomAD database, including 480 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 0.018 ( 32 hom., cov: 32)

Exomes 𝑓: 0.023 ( 448 hom. )

Consequence

CIZ1
NM_001131016.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.883

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0023836792).

BP6

Variant 9-128166354-C-T is Benign according to our data. Variant chr9-128166354-C-T is described in ClinVar as [Benign]. Clinvar id is 413837.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128166354-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0184 (2807/152192) while in subpopulation NFE AF= 0.0258 (1754/67996). AF 95% confidence interval is 0.0248. There are 32 homozygotes in gnomad4. There are 1352 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd at 2808 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CIZ1	NM_001131016.2 linkuse as main transcript	c.2540G>A	p.Arg847Gln	missense_variant	17/17	ENST00000372938.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CIZ1	ENST00000372938.10 linkuse as main transcript	c.2540G>A	p.Arg847Gln	missense_variant	17/17	1	NM_001131016.2	P2	Q9ULV3-1

Frequencies

GnomAD3 genomes

AF:

0.0185

AC:

2808

AN:

152074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00430

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.0174

Gnomad ASJ

AF:

0.0449

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0130

Gnomad FIN

AF:

0.0316

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0258

Gnomad OTH

AF:

0.0163

GnomAD3 exomes

AF:

0.0200

AC:

3336

AN:

166696

Hom.:

AF XY:

0.0200

AC XY:

1769

AN XY:

88452

show subpopulations

Gnomad AFR exome

AF:

0.00374

Gnomad AMR exome

AF:

0.0141

Gnomad ASJ exome

AF:

0.0452

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0142

Gnomad FIN exome

AF:

0.0270

Gnomad NFE exome

AF:

0.0253

Gnomad OTH exome

AF:

0.0250

GnomAD4 exome

AF:

0.0232

AC:

32695

AN:

1409270

Hom.:

448

Cov.:

AF XY:

0.0229

AC XY:

15944

AN XY:

695976

show subpopulations

Gnomad4 AFR exome

AF:

0.00396

Gnomad4 AMR exome

AF:

0.0141

Gnomad4 ASJ exome

AF:

0.0472

Gnomad4 EAS exome

AF:

0.0000815

Gnomad4 SAS exome

AF:

0.0138

Gnomad4 FIN exome

AF:

0.0280

Gnomad4 NFE exome

AF:

0.0247

Gnomad4 OTH exome

AF:

0.0234

GnomAD4 genome

AF:

0.0184

AC:

2807

AN:

152192

Hom.:

Cov.:

AF XY:

0.0182

AC XY:

1352

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.00429

Gnomad4 AMR

AF:

0.0173

Gnomad4 ASJ

AF:

0.0449

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0131

Gnomad4 FIN

AF:

0.0316

Gnomad4 NFE

AF:

0.0258

Gnomad4 OTH

AF:

0.0161

Alfa

AF:

0.0253

Hom.:

132

Bravo

AF:

0.0172

TwinsUK

AF:

0.0216

AC:

ALSPAC

AF:

0.0223

AC:

ESP6500AA

AF:

0.00460

AC:

ESP6500EA

AF:

0.0243

AC:

207

ExAC

AF:

0.0144

AC:

1669

Asia WGS

AF:

0.00347

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Dystonic disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 25, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.57

Cadd

Benign

Dann

Uncertain

1.0

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.45

LIST_S2

Uncertain

0.86

D;D;D;D;D;.;D;.;D;D

MetaRNN

Benign

0.0024

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

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

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

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.36

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

REVEL

Benign

0.034

Sift

Benign

0.061

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

Sift4G

Uncertain

0.038

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

Polyphen

0.12

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

Vest4

0.057

MPC

0.35

ClinPred

0.021

GERP RS

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Varity_R

0.032

gMVP

0.51

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