rs11549263

Variant names:

• chr9-128178842-T-C
• rs11549263
• NM_001131016.2:c.1365A>G

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001131016.2(CIZ1):​c.1365A>G​(p.Val455Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00967 in 1,614,230 control chromosomes in the GnomAD database, including 92 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0069 (6 hom., cov: 33)
  • Exomes 𝑓: 0.010 (86 hom.)
• Consequence: CIZ1 NM_001131016.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -6.86
• Publications: 8 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 9-128178842-T-C is Benign according to our data. Variant chr9-128178842-T-C is described in ClinVar as Benign. ClinVar VariationId is 413838.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-6.86 with no splicing effect.
• BS2: High AC in GnomAd4 at 1044 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001131016.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIZ1	NM_001131016.2	MANE Select	c.1365A>G	p.Val455Val	synonymous	Exon 8 of 17	NP_001124488.1
	CIZ1	NM_001257975.2		c.1455A>G	p.Val485Val	synonymous	Exon 8 of 18	NP_001244904.1
	CIZ1	NM_012127.3		c.1365A>G	p.Val455Val	synonymous	Exon 8 of 17	NP_036259.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIZ1	ENST00000372938.10	TSL:1 MANE Select	c.1365A>G	p.Val455Val	synonymous	Exon 8 of 17	ENSP00000362029.5
	CIZ1	ENST00000415526.5	TSL:1	c.1131A>G	p.Val377Val	synonymous	Exon 6 of 15	ENSP00000398011.1
	CIZ1	ENST00000372954.5	TSL:1	c.1125A>G	p.Val375Val	synonymous	Exon 8 of 17	ENSP00000362045.1

Frequencies

GnomAD3 genomes AF: 0.00687 AC: 1046 AN: 152220 Hom.: 6 Cov.: 33

Gnomad AFR AF: 0.00157

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.00517

Gnomad ASJ AF: 0.00778

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0149

Gnomad FIN AF: 0.00461

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0107

Gnomad OTH AF: 0.00812

GnomAD2 exomes AF: 0.00765 AC: 1923 AN: 251482 AF XY: 0.00866

Gnomad AFR exome AF: 0.00123

Gnomad AMR exome AF: 0.00182

Gnomad ASJ exome AF: 0.00635

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00485

Gnomad NFE exome AF: 0.0107

Gnomad OTH exome AF: 0.00423

GnomAD4 exome AF: 0.00996 AC: 14566 AN: 1461892 Hom.: 86 Cov.: 34 AF XY: 0.0101 AC XY: 7375 AN XY: 727246

African (AFR) AF: 0.00146 AC: 49 AN: 33480

American (AMR) AF: 0.00203 AC: 91 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00662 AC: 173 AN: 26136

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39700

South Asian (SAS) AF: 0.0137 AC: 1178 AN: 86258

European-Finnish (FIN) AF: 0.00487 AC: 260 AN: 53420

Middle Eastern (MID) AF: 0.00503 AC: 29 AN: 5768

European-Non Finnish (NFE) AF: 0.0111 AC: 12317 AN: 1112010

Other (OTH) AF: 0.00768 AC: 464 AN: 60396

GnomAD4 genome AF: 0.00685 AC: 1044 AN: 152338 Hom.: 6 Cov.: 33 AF XY: 0.00667 AC XY: 497 AN XY: 74498

African (AFR) AF: 0.00156 AC: 65 AN: 41584

American (AMR) AF: 0.00516 AC: 79 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00778 AC: 27 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.0147 AC: 71 AN: 4832

European-Finnish (FIN) AF: 0.00461 AC: 49 AN: 10622

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

European-Non Finnish (NFE) AF: 0.0107 AC: 726 AN: 68020

Other (OTH) AF: 0.00803 AC: 17 AN: 2116

Alfa AF: 0.00760 Hom.: 8

Bravo AF: 0.00638

Asia WGS AF: 0.00520 AC: 18 AN: 3478

EpiCase AF: 0.0100

EpiControl AF: 0.0114

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Dystonic disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	4.0
DANN	Benign	0.42
PhyloP100		-6.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs11549263; hg19: chr9-130941121; COSMIC: COSV99477135; COSMIC: COSV99477135;