Variant 9-128169142-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The ENST00000372938.10(CIZ1):c.2205C>T(p.Asp735=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0204 in 1,614,016 control chromosomes in the GnomAD database, including 383 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 21 hom., cov: 32)

Exomes 𝑓: 0.021 ( 362 hom. )

Consequence

CIZ1
ENST00000372938.10 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.506

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 9-128169142-G-A is Benign according to our data. Variant chr9-128169142-G-A is described in ClinVar as [Benign]. Clinvar id is 240852.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128169142-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.506 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0142 (2159/152182) while in subpopulation NFE AF= 0.0218 (1481/68006). AF 95% confidence interval is 0.0209. There are 21 homozygotes in gnomad4. There are 987 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2159 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CIZ1	NM_001131016.2 linkuse as main transcript	c.2205C>T	p.Asp735=	synonymous_variant	14/17	ENST00000372938.10	NP_001124488.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CIZ1	ENST00000372938.10 linkuse as main transcript	c.2205C>T	p.Asp735=	synonymous_variant	14/17	1	NM_001131016.2	ENSP00000362029	P2	Q9ULV3-1

Frequencies

GnomAD3 genomes

AF:

0.0142

AC:

2161

AN:

152064

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00418

Gnomad AMI

AF:

0.0507

Gnomad AMR

AF:

0.0135

Gnomad ASJ

AF:

0.0147

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.0145

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0218

Gnomad OTH

AF:

0.0172

GnomAD3 exomes

AF:

0.0138

AC:

3425

AN:

249064

Hom.:

AF XY:

0.0137

AC XY:

1843

AN XY:

134824

show subpopulations

Gnomad AFR exome

AF:

0.00369

Gnomad AMR exome

AF:

0.0114

Gnomad ASJ exome

AF:

0.0180

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00235

Gnomad FIN exome

AF:

0.0146

Gnomad NFE exome

AF:

0.0207

Gnomad OTH exome

AF:

0.0153

GnomAD4 exome

AF:

0.0210

AC:

30757

AN:

1461834

Hom.:

362

Cov.:

AF XY:

0.0204

AC XY:

14811

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.00314

Gnomad4 AMR exome

AF:

0.0117

Gnomad4 ASJ exome

AF:

0.0165

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.00246

Gnomad4 FIN exome

AF:

0.0159

Gnomad4 NFE exome

AF:

0.0246

Gnomad4 OTH exome

AF:

0.0201

GnomAD4 genome

AF:

0.0142

AC:

2159

AN:

152182

Hom.:

Cov.:

AF XY:

0.0133

AC XY:

987

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.00417

Gnomad4 AMR

AF:

0.0134

Gnomad4 ASJ

AF:

0.0147

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.0145

Gnomad4 NFE

AF:

0.0218

Gnomad4 OTH

AF:

0.0171

Alfa

AF:

0.0187

Hom.:

Bravo

AF:

0.0139

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.0206

EpiControl

AF:

0.0236

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Dystonic disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 19, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

1.0

DANN

Benign

0.38

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

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