Variant rs45611034 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 NM_001131016.2(CIZ1):c.1957A>C(p.Arg653=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0215 in 1,605,114 control chromosomes in the GnomAD database, including 462 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.020 ( 36 hom., cov: 33)

Exomes 𝑓: 0.022 ( 426 hom. )

Consequence

CIZ1
NM_001131016.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.16

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=-0.72).

BP6

Variant 9-128170094-T-G is Benign according to our data. Variant chr9-128170094-T-G is described in ClinVar as [Benign]. Clinvar id is 413832.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128170094-T-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.16 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.02 (2870/143754) while in subpopulation AMR AF= 0.0286 (381/13318). AF 95% confidence interval is 0.0264. There are 36 homozygotes in gnomad4. There are 1373 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2870 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CIZ1	NM_001131016.2 linkuse as main transcript	c.1957A>C	p.Arg653=	synonymous_variant	12/17	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.1957A>C	p.Arg653=	synonymous_variant	12/17	1	NM_001131016.2	ENSP00000362029	P2	Q9ULV3-1

Frequencies

GnomAD3 genomes

AF:

0.0200

AC:

2871

AN:

143632

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00436

Gnomad AMI

AF:

0.161

Gnomad AMR

AF:

0.0287

Gnomad ASJ

AF:

0.0379

Gnomad EAS

AF:

0.000203

Gnomad SAS

AF:

0.0131

Gnomad FIN

AF:

0.0162

Gnomad MID

AF:

0.0762

Gnomad NFE

AF:

0.0275

Gnomad OTH

AF:

0.0279

GnomAD3 exomes

AF:

0.0189

AC:

4677

AN:

248022

Hom.:

AF XY:

0.0196

AC XY:

2636

AN XY:

134326

show subpopulations

Gnomad AFR exome

AF:

0.00388

Gnomad AMR exome

AF:

0.0166

Gnomad ASJ exome

AF:

0.0360

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0110

Gnomad FIN exome

AF:

0.0139

Gnomad NFE exome

AF:

0.0259

Gnomad OTH exome

AF:

0.0253

GnomAD4 exome

AF:

0.0216

AC:

31592

AN:

1461360

Hom.:

426

Cov.:

AF XY:

0.0217

AC XY:

15746

AN XY:

727022

show subpopulations

Gnomad4 AFR exome

AF:

0.00454

Gnomad4 AMR exome

AF:

0.0164

Gnomad4 ASJ exome

AF:

0.0365

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0111

Gnomad4 FIN exome

AF:

0.0145

Gnomad4 NFE exome

AF:

0.0237

Gnomad4 OTH exome

AF:

0.0226

GnomAD4 genome

AF:

0.0200

AC:

2870

AN:

143754

Hom.:

Cov.:

AF XY:

0.0197

AC XY:

1373

AN XY:

69638

show subpopulations

Gnomad4 AFR

AF:

0.00435

Gnomad4 AMR

AF:

0.0286

Gnomad4 ASJ

AF:

0.0379

Gnomad4 EAS

AF:

0.000203

Gnomad4 SAS

AF:

0.0129

Gnomad4 FIN

AF:

0.0162

Gnomad4 NFE

AF:

0.0275

Gnomad4 OTH

AF:

0.0281

Alfa

AF:

0.0231

Hom.:

Bravo

AF:

0.0191

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.0309

EpiControl

AF:

0.0303

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

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

9.3

DANN

Benign

0.64

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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