rs45518842

Variant names:

• chr9-128180530-T-C
• rs45518842
• NM_001131016.2:c.683-7A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• dystonia 23

  Inheritance: Unknown Classification: MODERATE Submitted by: Genomics England PanelApp
• inherited dystonia

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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	c.683-7A>G		splice_region_variant, intron_variant	Intron 6 of 16	ENST00000372938.10	NP_001124488.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0537 AC: 8172 AN: 152054 Hom.: 707 Cov.: 31

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

GnomAD2 exomes AF: 0.0180 AC: 4530 AN: 251194 AF XY: 0.0160

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 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.: 29 AF XY: 0.00776 AC XY: 5637 AN XY: 726078

African (AFR) AF: 0.195 AC: 6524 AN: 33410

American (AMR) AF: 0.0125 AC: 560 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00502 AC: 131 AN: 26110

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39692

South Asian (SAS) AF: 0.0296 AC: 2550 AN: 86184

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.0167 AC: 96 AN: 5762

European-Non Finnish (NFE) AF: 0.000458 AC: 508 AN: 1109566

Other (OTH) AF: 0.0155 AC: 933 AN: 60304

GnomAD4 genome AF: 0.0538 AC: 8184 AN: 152172 Hom.: 705 Cov.: 31 AF XY: 0.0524 AC XY: 3899 AN XY: 74420

African (AFR) AF: 0.181 AC: 7513 AN: 41454

American (AMR) AF: 0.0241 AC: 369 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00490 AC: 17 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.0320 AC: 154 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000691 AC: 47 AN: 68020

Other (OTH) AF: 0.0393 AC: 83 AN: 2114

Alfa AF: 0.0271 Hom.: 187

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

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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
PhyloP100		-1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs45518842; hg19: chr9-130942809;