Genetic Variant CIZ1:c.683-7A>G (chr9-128180530-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001131016.2(CIZ1):c.683-7A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0121 in 1,611,328 control chromosomes in the GnomAD database, including 1,477 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.054 ( 705 hom., cov: 31)

Exomes 𝑓: 0.0077 ( 772 hom. )

Consequence

CIZ1
NM_001131016.2 splice_region, intron

Scores

Splicing: ADA: 0.00002037

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.52

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 9-128180530-T-C is Benign according to our data. Variant chr9-128180530-T-C is described in ClinVar as [Benign]. Clinvar id is 413840.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIZ1	NM_001131016.2 link	c.683-7A>G		splice_region_variant, intron_variant	Intron 6 of 16	ENST00000372938.10	NP_001124488.1	Q9ULV3-1A0A024R885

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIZ1	ENST00000372938.10 link	c.683-7A>G		splice_region_variant, intron_variant	Intron 6 of 16	1	NM_001131016.2	ENSP00000362029.5		Q9ULV3-1

Frequencies

GnomAD3 genomes

AF:

0.0537

AC:

8172

AN:

152054

Hom.:

707

Cov.:

show subpopulations

Gnomad AFR

AF:

0.181

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0242

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0319

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000691

Gnomad OTH

AF:

0.0392

GnomAD3 exomes

AF:

0.0180

AC:

4530

AN:

251194

Hom.:

295

AF XY:

0.0160

AC XY:

2168

AN XY:

135754

show subpopulations

Gnomad AFR exome

AF:

0.182

Gnomad AMR exome

AF:

0.0114

Gnomad ASJ exome

AF:

0.00527

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0316

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000810

Gnomad OTH exome

AF:

0.00980

GnomAD4 exome

AF:

0.00775

AC:

11303

AN:

1459156

Hom.:

772

Cov.:

AF XY:

0.00776

AC XY:

5637

AN XY:

726078

show subpopulations

Gnomad4 AFR exome

AF:

0.195

Gnomad4 AMR exome

AF:

0.0125

Gnomad4 ASJ exome

AF:

0.00502

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0296

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000458

Gnomad4 OTH exome

AF:

0.0155

GnomAD4 genome

AF:

0.0538

AC:

8184

AN:

152172

Hom.:

705

Cov.:

AF XY:

0.0524

AC XY:

3899

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.181

Gnomad4 AMR

AF:

0.0241

Gnomad4 ASJ

AF:

0.00490

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0320

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000691

Gnomad4 OTH

AF:

0.0393

Alfa

AF:

0.0275

Hom.:

132

Bravo

AF:

0.0618

Asia WGS

AF:

0.0310

AC:

107

AN:

3478

EpiCase

AF:

0.000818

EpiControl

AF:

0.000830

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dystonic disorder

Benign:1

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.23

DANN

Benign

0.28

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000020

dbscSNV1_RF

Benign

0.0080

SpliceAI score (max)

0.010

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