rs45536439

chr9-128179172-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001131016.2(CIZ1):c.1035G>A(p.Ala345=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00778 in 1,613,952 control chromosomes in the GnomAD database, including 662 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.038 (344 hom., cov: 33)
  • Exomes 𝑓: 0.0046 (318 hom.)
• Consequence: CIZ1 NM_001131016.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -5.47

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 9-128179172-C-T is Benign according to our data. Variant chr9-128179172-C-T is described in ClinVar as [Benign]. Clinvar id is 413836.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-5.47 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CIZ1	NM_001131016.2	c.1035G>A	p.Ala345=	synonymous_variant	8/17	ENST00000372938.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CIZ1	ENST00000372938.10	c.1035G>A	p.Ala345=	synonymous_variant	8/17	1	NM_001131016.2	P2

Frequencies

GnomAD3 genomes AF: 0.0379 AC: 5765 AN: 152070 Hom.: 342 Cov.: 33

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0202

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.000848

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00129

Gnomad OTH AF: 0.0229

GnomAD3 exomes AF: 0.0106 AC: 2666 AN: 250376 Hom.: 156 AF XY: 0.00783 AC XY: 1060 AN XY: 135406

Gnomad AFR exome AF: 0.131

Gnomad AMR exome AF: 0.00920

Gnomad ASJ exome AF: 0.000497

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000229

Gnomad FIN exome AF: 0.000973

Gnomad NFE exome AF: 0.00127

Gnomad OTH exome AF: 0.00587

GnomAD4 exome AF: 0.00463 AC: 6771 AN: 1461764 Hom.: 318 Cov.: 34 AF XY: 0.00403 AC XY: 2933 AN XY: 727188

Gnomad4 AFR exome AF: 0.132

Gnomad4 AMR exome AF: 0.00973

Gnomad4 ASJ exome AF: 0.000459

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.000220

Gnomad4 FIN exome AF: 0.000806

Gnomad4 NFE exome AF: 0.00115

Gnomad4 OTH exome AF: 0.00894

GnomAD4 genome AF: 0.0380 AC: 5789 AN: 152188 Hom.: 344 Cov.: 33 AF XY: 0.0374 AC XY: 2786 AN XY: 74400

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.0201

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.000848

Gnomad4 NFE AF: 0.00129

Gnomad4 OTH AF: 0.0227

Alfa AF: 0.0171 Hom.: 86

Bravo AF: 0.0427

Asia WGS AF: 0.00953 AC: 33 AN: 3478

EpiCase AF: 0.00153

EpiControl AF: 0.000889

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

CIZ1-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 03, 2020

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). -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 14, 2018

- -

Dystonic disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
Cadd	Benign	6.2
Dann	Benign	0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs45536439; hg19: chr9-130941451;